Methods and systems for OCT guided glaucoma surgery

ABSTRACT

Disclosed herein are systems and methods for aiding a surgeon to perform a surgical procedure on an eye. The surgical procedure includes inserting an elongate probe from an opening into the eye across an anterior chamber to a target tissue region comprising a trabecular meshwork and a Schlemm&#39;s canal. Exemplary systems include an optical microscope for the surgeon to view the eye with a microscope image during the procedure; an optical coherence tomography (OCT) apparatus configured to perform an OCT scan of a target location in the target tissue region during the procedure; and an image processing apparatus configured to generate an augmented image by overlaying an OCT image of target location and a graphical visual element identifying the locations, wherein the graphical visual element is registered with the microscope image to aid the surgeon in advancing a distal end of the elongate probe to the target location.

CROSS-REFERENCE

This application claims the benefit of provisional patent applicationU.S. Prov. Ser. App. No. 62/521,310 filed Jun. 16, 2017, entitled“Methods and Systems for OCT Guided Glaucoma Surgery”. This applicationis also related to U.S. application Ser. No. 15/868,904 filed Jan. 11,2018, entitled “Methods and Systems for OCT Guided Glaucoma Surgery”.Each of these applications are incorporated herein by reference in theirentirety.

BACKGROUND

Glaucoma is a disease of the eye in which intraocular structurescritical to vision is irreversibly damaged. These structures includeportions of the retina and especially portions of the optic nerve.Glaucoma, a treatable condition, is cited as the second leading cause ofblindness in the United States. Several million people are affected.There are two major types of glaucoma, open angle glaucoma, and closedangle glaucoma. Open angle glaucoma, the most common type of glaucoma,occurs when the normal appearing outflow pathways malfunction such thatthe eye does not adequately drain fluid which results in an intraocularelevation of pressure. Elevated intraocular pressure (IOP) in mostopen-angle glaucoma is due to an obstruction of aqueous outflowlocalized predominantly at the juxtacanalicular trabecular meshwork (TM)and the inner wall of Schlemm's canal (SC).

Treatments for elevated IOP due to outflow obstruction include topicaland systemic medications, office-based laser procedures, and riskinherent invasive surgical procedures (trabeculectomy/tube shunt).Examples of laser procedures include argon laser trabeculoplasty (ALT)and selective laser trabeculoplasty (SLT). More recently less invasivesurgical procedures have been introduced into the treatment paradigms,commonly termed minimally invasive glaucoma surgery (MIGS), ormicro-invasive glaucoma surgical procedures. Current approaches of IOPreduction by MIGS include increasing trabecular outflow by bypassing thejuxtacanalicular trabecular meshwork (TM) and inner wall of SC,increasing uveoscleral outflow via suprachoroidal pathways, reducingaqueous production from the ciliary body, or creating an external,subconjunctival/suprascleral drainage pathway.

The general concept of MIGS is typically to bypass outflow obstructionand enable resumption of flow via the eye's intrinsic outflow systemwhich is often intact and functional beyond the region of outflowobstruction, rather than creating alternative pathways which may havesignificantly greater short and/or long term risks.

MIGS procedures often involve visualization and access to theintraocular outflow system. Due to the shape of the cornea and thelocation of intraocular structures related to MIGS procedures in theregion where the iris appears to meet the peripheral cornea, totalinternal reflection occurs and can prevent a surgeon from viewing thoseoutflow structures that reside beyond the “critical angle” of theoptical pathway, which in the context of the anterior chamber surgicalprocedures disclosed herein, can also be referred to as the “criticalangle” of the anterior chamber optical viewing pathway. According tosome embodiments, the optical pathway as disclosed herein can refer tothe viewing of the anterior chamber angle structures and not the opticalpathway of the eye's visual system, e.g. near the center of the corneato the macula. As such, devices to allow visualization of those outflowstructures are often necessary for a surgeon to perform MIGS procedures.Goniolenses, both direct (allowing a straight optical pathway forviewing those structures) and indirect (using mirrors to view thosestructures) function by overcoming total internal reflection. However,intraoperative use of goniolenses can require significant dexterity anda steep learning curve, which may limit successful MIGS procedures tocertain skilled surgeons in at least some instances.

In at least some of these surgical procedures, a surgical opening iscreated through the trabecular meshwork and the inner wall of Schlemm'scanal to enable improved fluidic access into Schlemm's canal in order toreduce intra ocular pressure. Prior approaches to accurately targetSchlemm's canal are often less than ideal. Thus, it would be beneficialto provide methods and apparatuses that provide improved consistency andaccuracy in targeting Schlemm's canal and other structures of the eye.Also, work in relation to the present disclosure suggests that at leastsome of the prior approaches may result in openings into Schlemm's canalat less than ideal locations, for example at locations which are faraway from collector channels. Alternative MIGS devices which bypassSchlemm's canal and drain aqueous fluid into the suprachoroidal spacecan also benefit from targeted location placement by improvingvisualization of adjacent ocular structures. Examples of such implantdevices include the intracanalicular iStent®, and iStent inject and thesuprachoroidal CyPass® microstent. Excimer laser trabeculostomy (ELT)which creates patent channel openings into Schlemm's canal can alsobenefit from improved targeting and visualization of structures in theeye.

Current methods and apparatus for viewing structures of the eye near theirido-corneal angle, such as the trabecular meshwork and scleral spur,can be less than ideal in at least some instances. For example, agoniolens can be somewhat more difficult to use than would be ideal, andit would be beneficial to provide improved methods an apparatus forviewing the structures of the eye near the irido-corneal angle duringsurgery in this region.

In light of the above, it would be helpful to have improved methods andapparatus for imaging the eye during surgical procedures, targetingoutflow structures of the eye such as Schlemm's canal, and determiningtarget locations for openings through the trabecular meshwork and intoSchlemm's canal to improve flow.

SUMMARY

The methods and apparatus disclosed herein allow glaucoma surgery of theoutflow structures, including MIGS and many varieties thereof, to beperformed without a goniolens. According to an aspect of the invention,an ophthalmic surgeon can identify these outflow structures and operateon these structures through virtual images and representations of thestructures and the surgical tools generated using optical coherencetomography (OCT) scanning.

In one aspect, a system for aiding a physician to perform a surgicalprocedure on an eye is provided. The operation procedure comprisesinserting an elongate probe from an opening into the eye across ananterior chamber to a target tissue region comprising a trabecularmeshwork and a Schlemm's canal. The system comprises: an opticalmicroscope for the surgeon to view the eye with a microscope imageduring the procedure; one or more optical coherence tomography (OCT)apparatus configured to perform OCT scans of one or more targetlocations in the target tissue region in real time during the procedure;and an image processing apparatus configured to generate a plurality ofaugmented images (real and virtual) by enabling viewing of and in somecases overlaying (1) one or more OCT images of the one or more targetlocations and/or (2) a plurality of graphical visual elementsidentifying the one or more target locations, wherein the plurality ofgraphical visual elements is registered with the real microscope imageto aid the physician in advancing a distal end of the elongate probe tothe one or more target locations.

In another aspect, embodiments of the present invention encompassmethods of performing a surgical procedure on an eye of a patient.Exemplary methods may include viewing a real-time view on a viewingdevice, where the real-time view includes (i) a microscope view of theeye and (ii) an augmented image having the microscope view or amicroscope image of the eye. The augmented image may also have anoptical coherence tomography (OCT) image of a target tissue region. TheOCT image can be registered with the microscope view or the microscopeimage. The OCT image can enable identification of a target locationpositioned in the target tissue, and wherein an actual target locationis not visible in the microscope view or the microscope image. Exemplarymethods may further include advancing a distal end of an elongate probewithin an anterior chamber of the eye toward the target tissue regionwhile viewing the microscope view or the augmented image on the viewingdevice, where the distal end of the elongate probe is initially visiblein the microscope view or the microscope image and thereafter becomesnot visible in the microscope view or the microscope image due to totalinternal reflection in the region of the eye wherein lies the targettissue. Exemplary methods may also include performing the surgicalprocedure at the actual target location using the elongate probe whilethe distal end of the elongate probe is not visible in the microscopeview or the microscope image, and while perceiving information from theaugmented image regarding a relative position of the distal end of theelongate probe with respect to the target location.

According to some embodiments, a graphical visual element identifyingthe target location can be overlaid the microscope view or themicroscope image. In some embodiments, the real-time view includes theaugmented image having the microscope view of the eye, the OCT image isregistered with the microscope view, and the actual target location isnot visible in the microscope view. A graphical visual element may beoverlaid the microscope view. In some embodiments, the advancing stepincludes advancing the distal end of the elongate probe within theanterior chamber of the eye toward the target tissue region whileviewing the augmented image on the viewing device, where the distal endof the elongate probe is initially visible in the microscope view andthereafter becomes not visible in the microscope view due to totalinternal reflection in the region of the eye wherein lies the targettissue region. In some embodiments, the performing step includesperforming the surgical procedure at the target location using theelongate probe while the distal end of the elongate probe is not visiblein the microscope view, and while perceiving information from themicroscope view regarding a relative position of the distal end of theelongate probe with respect to the target location. In some embodiments,the real-time view includes the augmented image, and the OCT imageregistered with the microscope view or the microscope image includesinformation regarding Schlemm's canal and the collector channel system.In some embodiments, the real-time view includes the augmented image,and the OCT image registered with the microscope view or the microscopeimage includes information regarding a relative position of the distalend of the elongate probe with respect to the target location.

In some instances, a graphical visual element corresponding to thedistal end of the elongate probe is overlaid the microscope view or themicroscope image, and the advancing step includes advancing the distalend of the elongate probe toward the target tissue region, while viewingthe graphical visual element corresponding to the distal end of theelongate probe and the graphical visual element corresponding to thetarget location on the augmented image, as the distal end of theelongate probe approaches and contacts the target tissue region. In someembodiments, a graphical visual element corresponding to the distal endof the elongate probe and a graphical visual element corresponding to asurface of the trabecular meshwork of the eye are overlaid themicroscope view or the microscope image, and the method includesdetermining there is contact between the distal end of the elongateprobe and the surface of the trabecular meshwork when the graphicalvisual element corresponding to the distal end of the elongate probe andthe graphical visual element corresponding to a surface of thetrabecular meshwork are sufficiently close. In some embodiments, agraphical visual element corresponding to a surface of a trabecularmeshwork and a graphical visual element corresponding to ajuxtacanalicular trabecular meshwork of the eye are overlaid themicroscope view or the microscope image, and the method includesdetermining whether a trabecular meshwork of the eye is sufficientlycompressed when the graphical visual element corresponding to surface ofthe trabecular meshwork and the graphical visual element correspondingto the juxtacanalicular trabecular meshwork are sufficiently close. Insome embodiments, a graphical visual element corresponding to an innerwall of Schlemm's canal of the eye is overlaid the microscope view orthe microscope image, and the method includes determining that the innerwall of Schlemm's canal has been penetrated when the graphical visualelement corresponding to the inner wall of Schlemm's canal disappearsfrom the microscope view or the microscope image.

In some instances, a guidance arrow is overlaid the microscope view orthe microscope image, and the guidance arrow points to the graphicalvisual element identifying the target location. In some instances, aguidance arrow is overlaid the microscope view or the microscope image,and the guidance arrow points to the graphical visual elementidentifying the target location. In some methods, the advancing stepincludes advancing the distal end of the elongate probe toward thetarget location while using the guidance arrow as a guide. In somemethods, the performing step includes ablating the target location withlaser pulses emanating from the elongate probe, and following thecreation of a channel which connects the anterior chamber to a lumen ofSchlemm's canal at the target location, a second guidance arrow isoverlaid the microscope view of the microscope image, where the secondguidance arrow points to a second graphical visual element identifying asecond target location of the eye, and methods may further includeadvancing the distal end of the elongate probe toward the second targetlocation while using the second guidance arrow as a guide. Methods mayalso include ablating the second target location with the elongateprobe.

In some embodiments, the viewing device can be a display device, amicroscope device, a heads up display, a viewing monitor, a virtualreality viewing device, or an augmented reality viewing device. In someembodiments, a graphical visual element identifying the distal end ofthe elongate probe can be overlaid the microscope view or the microscopeimage, and the relative position of the distal end of the elongate probewith respect to the target location can be based on a relative positionof the distal end of the elongate probe with respect to the graphicalvisual element identifying the target location. In some instances, theactual target location is not visible in the microscope view or themicroscope image due to total internal reflection in the eye. In someinstances, the target location is determined based on a preoperativeoptical coherence tomography (OCT) image, an intra-operative opticalcoherence tomography (OCT) image, a preoperative optical coherencetomography (OCT) image and an intra-operative optical coherencetomography (OCT) image, or a decision by a surgeon. In some instances,the preoperative OCT image shows Schlemm's canal and networks ofcollector channels of the eye, and the target location is determinedbased on the preoperative OCT image. In some instances, the targetlocation is determined based on a microscope-based OCT image, afiberoptic-based OCT image, or a microscope-based OCT image and afiberoptic-based OCT image.

In still another aspect, embodiments of the present invention encompassmethods of assisting a surgeon to perform a surgical procedure on an eyeof a patient. In such procedures, the surgeon may use an elongate probehaving a distal end. Exemplary methods include providing a real-timeview to the surgeon. The real-time view can include (i) a microscopeview of the eye and (ii) an augmented image having the microscope viewor a microscope image of the eye. The augmented image may furtherinclude an optical coherence tomography (OCT) image of a target tissueregion. The OCT image can be registered with the microscope view or themicroscope image. The OCT image can enable identification of a targetlocation positioned in the target tissue region. An actual targetlocation may not be visible in the microscope view or the microscopeimage. The augmented image can enable the surgeon to perceiveinformation regarding a relative position of the distal end of theelongate probe with respect to the target location when the distal endof the elongate probe is not visible in the microscope view or themicroscope image.

In some instances, a graphical visual element identifying the targetlocation can be overlaid the microscope view or the microscope image. Insome instances, the real-time view includes the augmented image havingthe microscope view of the eye, the OCT image is registered with themicroscope view, the actual target location is not visible in themicroscope view, and the augmented image enables the surgeon to perceiveinformation regarding a relative position of the distal end of theelongate probe with respect to the target location when the distal endof the elongate probe is not visible in the microscope view. A graphicalvisual element can be overlaid the microscope view. According to someembodiments, the real-time view includes the augmented image having themicroscope image of the eye, the OCT image is registered with themicroscope image, the actual target location is not visible in themicroscope image, and the augmented image enables the surgeon toperceive information regarding a relative position of the distal end ofthe elongate probe with respect to the target location when the distalend of the elongate probe is not visible in the microscope image. Agraphical visual element can be overlaid the microscope image.

According to some embodiments, the real-time view includes the augmentedimage, and the OCT image registered with the microscope view or themicroscope image includes information regarding Schlemm's canal and thecollector channel system. According to some embodiments, the real-timeview includes the augmented image, and the OCT image registered with themicroscope view or the microscope image includes information regarding arelative position of the distal end of the elongate probe with respectto the target location. In some instances, a graphical visual elementcorresponding to the distal end of the elongate probe is overlaid themicroscope view or the microscope image, and the information regarding arelative position of the distal end of the elongate probe with respectto the target location is provided by the graphical visual elementcorresponding to the distal end of the elongate probe and the graphicalvisual element corresponding to the target location. In some instances,a graphical visual element corresponding to the distal end of theelongate probe and a graphical visual element corresponding to a surfaceof the trabecular meshwork of the eye are overlaid the microscope viewor the microscope image, and the augmented image enables the surgeon todetermine whether there is contact between the distal end of theelongate probe and the surface of the trabecular meshwork based onrelative positions of the graphical visual element corresponding to thedistal end of the elongate probe and the graphical visual elementcorresponding to a surface of the trabecular meshwork. In someinstances, a graphical visual element corresponding to a surface of thetrabecular meshwork and a graphical visual element corresponding to ajuxtacanalicular trabecular meshwork of the eye are overlaid themicroscope view or the microscope image, and the augmented image enablesthe surgeon to determine whether a trabecular meshwork of the eye issufficiently compressed based on relative positions of the graphicalvisual element corresponding to the surface of the trabecular meshworkand the graphical visual element corresponding to the juxtacanaliculartrabecular meshwork. In some instances, a graphical visual elementcorresponding to an inner wall of Schlemm's canal of the eye is overlaidthe microscope view or the microscope image, and the augmented imageenables the surgeon to determine whether the inner wall of Schlemm'scanal has been penetrated based on whether when the graphical visualelement corresponding to an inner wall of Schlemm's canal is present inor absent from the microscope view or the microscope image.

According to some embodiments, a guidance arrow is overlaid themicroscope view or the microscope image, and the guidance arrow pointsto the graphical visual element identifying the target location.According to some embodiments, a guidance arrow is overlaid themicroscope view or the microscope image, the guidance arrow points tothe graphical visual element identifying the target location, andfollowing ablation of the target location, a second guidance arrow isoverlaid the microscope view of the microscope image, and the secondguidance arrow points to a second graphical visual element identifying asecond target location of the eye. In some instances, the real-time viewis provided to the surgeon by a display device, a microscope device, aheads up display, a viewing monitor, a virtual reality viewing device,or an augmented reality viewing device. In some instances, a graphicalvisual element identifying the distal end of the elongate probe isoverlaid the microscope view or the microscope image, and the relativeposition of the distal end of the elongate probe with respect to thetarget location is based on a relative position of the identifying thedistal end of the elongate probe with respect to the graphical visualelement identifying the target location. In some instances, the actualtarget location is not visible in the microscope view or the microscopeimage due to total internal reflection in the eye. In some instances,the target location is determined based on a preoperative opticalcoherence tomography (OCT) image, an intra-operative optical coherencetomography (OCT) image, a preoperative optical coherence tomography(OCT) image and an intra-operative optical coherence tomography (OCT)image, or a decision by the surgeon. In some instances, the preoperativeOCT image shows Schlemm's canal and networks of collector channels ofthe eye, and the target location is determined based on the preoperativeOCT image.

According to some embodiments, a target location can be determined basedon a microscope-based OCT image, a fiberoptic-based OCT image, or amicroscope-based OCT image and a fiberoptic-based OCT image. In someinstances, methods may further include providing the surgeon with anotification upon detection of sufficient compression of a trabecularmeshwork of the eye, where sufficient compression is detected based onrelative positions of a graphical visual element corresponding to asurface of the trabecular meshwork and a graphical visual elementcorresponding to the juxtacanalicular trabecular meshwork. In someinstances, methods may also include automatically initiating delivery oflaser ablation energy to the actual target location upon detection ofsufficient compression of the trabecular meshwork of the eye. In somecases, methods can include providing the surgeon with a notificationupon detection of penetration of an inner wall of Schlemm's canal, wherepenetration of the inner wall of Schlemm's canal is detected by theelongate probe and demonstrated in the real-time view based on whether agraphical visual element corresponding the inner wall of Schlemm's canalis present in or absent from the augmented image. In some cases, methodsmay include automatically terminating delivery of laser ablation energyto the actual target location upon detection of penetration of an innerwall of Schlemm's canal.

In another aspect, embodiments of the present invention encompasscomputer program products for aiding a surgeon to perform a surgicalprocedure on an eye of a patient, for example where the surgeon uses anelongate probe having a distal end. The computer program product can beembodied on a non-transitory tangible computer readable medium.Exemplary computer program products include computer-executable code forgenerating a real-time view for viewing by the surgeon, where thereal-time view includes (i) a microscope view of the eye and (ii) anaugmented image having the microscope view or a microscope image of theeye. The augmented image can further include an optical coherencetomography (OCT) image of a target tissue region. The OCT image can beregistered with the microscope view or the microscope image. The OCTimage can enable identification of a target location positioned in thetarget tissue region. An actual target location may not be visible inthe microscope view or the microscope image. The augmented image canenable the surgeon to perceive information regarding a relative positionof the distal end of the elongate probe with respect to the targetlocation when the distal end of the elongate probe is not visible in themicroscope view or the microscope image. In some cases, a graphicalvisual element identifying a target location positioned in the targettissue region is overlaid the microscope view or the microscope image.According to some embodiments, the real-time view includes the augmentedimage having the microscope view of the eye, the OCT image is registeredwith the microscope view, the actual target location is not visible inthe microscope view, and the augmented image enables the surgeon toperceive information regarding a relative position of the distal end ofthe elongate probe with respect to the target location when the distalend of the elongate probe is not visible in the microscope view. Agraphical visual element can be overlaid the microscope view. Accordingto some embodiments, the real-time view includes the augmented imagehaving the microscope image of the eye, the OCT image is registered withthe microscope image, the actual target location is not visible in themicroscope image, and the augmented image enables the surgeon toperceive information regarding a relative position of the distal end ofthe elongate probe with respect to the target location when the distalend of the elongate probe is not visible in the microscope image. Thegraphical visual element can be overlaid the microscope image.

In some instances, the real-time view includes the augmented image, andthe OCT image registered with the microscope view or the microscopeimage includes information regarding Schlemm's canal and the collectorchannel system. In some instances, the real-time view includes theaugmented image, and the OCT image registered with the microscope viewor the microscope image includes information regarding a relativeposition of the distal end of the elongate probe with respect to thetarget location. In some instances, a graphical visual elementcorresponding to the distal end of the elongate probe is overlaid themicroscope view or the microscope image, and the information regarding arelative position of the distal end of the elongate probe with respectto the target location is provided by the graphical visual elementcorresponding to the distal end of the elongate probe and the graphicalvisual element corresponding to the target location. In some instances,a graphical visual element corresponding to the distal end of theelongate probe and a graphical visual element corresponding to a surfaceof the trabecular meshwork of the eye are overlaid the microscope viewor the microscope image, and the augmented image enables the surgeon todetermine whether there is contact between the distal end of theelongate probe and the surface of the trabecular meshwork based onrelative positions of the graphical visual element corresponding to thedistal end of the elongate probe and the graphical visual elementcorresponding to a surface of the trabecular meshwork. In someinstances, a graphical visual element corresponding to a surface of atrabecular meshwork and a graphical visual element corresponding to ajuxtacanalicular trabecular meshwork of the eye are overlaid themicroscope view or the microscope image, and the augmented image enablesthe surgeon to determine whether a trabecular meshwork of the eye issufficiently compressed based on relative positions of the graphicalvisual element corresponding to the surface of the trabecular meshworkand the graphical visual element corresponding to the juxtacanaliculartrabecular meshwork. In some instances, a graphical visual elementcorresponding to an inner wall of Schlemm's canal of the eye is overlaidthe microscope view or the microscope image, and the augmented imageenables the surgeon to determine whether the inner wall Schlemm's canalhas been penetrated based on whether when the graphical visual elementcorresponding to the inner wall of Schlemm's canal is present in orabsent from the microscope view or the microscope image.

According to some embodiments, a guidance arrow can be overlaid themicroscope view or the microscope image, and the guidance arrow canpoint to the graphical visual element identifying the target location.In some embodiments, a guidance arrow can be overlaid the microscopeview or the microscope image, the guidance arrow can point to thegraphical visual element identifying the target location, and followingablation of the target location, a second guidance arrow can be overlaidthe microscope view of the microscope image, and the second guidancearrow can point to a second graphical visual element identifying asecond target location of the eye. In some instances, the real-time viewcan be provided to the surgeon by a display device, a microscope device,a heads up display, a viewing monitor, a virtual reality viewing device,or an augmented reality viewing device. In some instances, a graphicalvisual element identifying the distal end of the elongate probe can beoverlaid the microscope view or the microscope image, and the relativeposition of the distal end of the elongate probe with respect to thetarget location is based on a relative position of the identifying thedistal end of the elongate probe with respect to the graphical visualelement identifying the target location. In some cases, the actualtarget location may not be visible in the microscope view or themicroscope image due to total internal reflection in the eye.

According to some embodiments, a target location can be determined basedon a preoperative optical coherence tomography (OCT) image, anintra-operative optical coherence tomography (OCT) image, or apreoperative optical coherence tomography (OCT) image and anintra-operative optical coherence tomography (OCT) image. In some cases,a preoperative OCT image can show Schlemm's canal and networks ofcollector channels of the eye, and the target location can be determinedbased on the preoperative OCT image. In some cases, a target locationcan be determined based on a microscope-based OCT image, afiberoptic-based OCT image, a microscope-based OCT image and afiberoptic-based OCT image, or a decision by the surgeon. A computerprogram product can further include computer-executable code forproviding the surgeon with a notification upon detection of sufficientcompression of a trabecular meshwork of the eye, wherein sufficientcompression is detected based on relative positions of a graphicalvisual element corresponding to a surface of a trabecular meshwork and agraphical visual element corresponding to the juxtacanaliculartrabecular meshwork. In some cases, a computer program product canfurther include computer-executable code for automatically initiatingdelivery of laser ablation energy to the actual target location upondetection of sufficient compression of the trabecular meshwork of theeye. In some cases, a computer program product can further includecomputer-executable code for providing the surgeon with a notificationupon detection of penetration of an inner wall of Schlemm's canal, wherepenetration of the inner wall of Schlemm's canal is detected by anelongate probe and demonstrated in a real-time view based on whether agraphical visual element corresponding the inner wall of Schlemm's canalis present in or absent from the augmented image. In some cases, acomputer program product can further include computer-executable codefor automatically terminating delivery of laser ablation energy to theactual target location upon detection of penetration of an inner wall ofSchlemm's canal.

In another aspect, embodiments of the present invention encompassmethods of performing a surgical procedure on an eye of a patient, whereexemplary methods include viewing a real-time view on a viewing device,where the real-time view includes an augmented image having themicroscope view or a microscope image of the eye. The augmented imagecan further include an optical coherence tomography (OCT) image of atarget tissue region. The OCT image can include information regardingSchlemm's canal and the collector channel system and can be registeredwith the microscope view or the microscope image. In some cases, agraphical visual element identifying a target location positioned in thetarget tissue region can be overlaid the microscope view or themicroscope image. An actual target location may not be visible in themicroscope view or the microscope image. Exemplary methods may alsoinclude advancing a distal end of an elongate probe within an anteriorchamber of the eye toward the target tissue region while viewing theaugmented image on the viewing device, where the distal end of theelongate probe is initially visible in the microscope view or themicroscope image and thereafter becomes not visible in the microscopeview or the microscope image due to total internal reflection in theregion of the eye wherein lies the target tissue. Exemplary methods mayalso include performing the surgical procedure at the actual targetlocation using the elongate probe while the distal end of the elongateprobe is not visible in the microscope view or the microscope image, andwhile perceiving information from the augmented image regarding arelative position of the distal end of the elongate probe with respectto the target location.

In still another aspect, embodiments of the present invention encompassmethods of performing a surgical procedure on an eye of a patient, whereexemplary methods include viewing a real-time view on a viewing device,where the real-time view includes an augmented image having themicroscope view or a microscope image of the eye. The augmented imagecan further include an optical coherence tomography (OCT) image of atarget tissue region. The OCT image can be registered with themicroscope view or the microscope image. A graphical visual elementidentifying a target location positioned in the target tissue region canbe overlaid the microscope view or the microscope image. An actualtarget location may not be visible in the microscope view or themicroscope image. Exemplary methods may also include advancing a distalend of an elongate probe within an anterior chamber of the eye towardthe target tissue region while viewing the augmented image on theviewing device, the distal end of the elongate probe is initiallyvisible in the microscope view or the microscope image and thereafterbecomes not visible in the microscope view or the microscope image dueto total internal reflection in the region of the eye wherein lies thetarget tissue. An OCT image registered with the microscope view or themicroscope image can include regarding a relative position of the distalend of the elongate probe with respect to the target location. Exemplarymethods may also include performing the surgical procedure at the actualtarget location using the elongate probe while the distal end of theelongate probe is not visible in the microscope view or the microscopeimage, and while perceiving the information regarding the relativeposition of the distal end of the elongate probe with respect to thetarget location.

In still another aspect, embodiments of the present invention encompasscomputer systems to assist a surgeon in performing a surgical procedureon an eye of a patient. During the surgical procedure, the surgeon canuse an elongate probe having a distal end. Exemplary computer systemscan include a processor, an electronic storage location operativelycoupled with the processor, and processor executable code stored on theelectronic storage location and embodied in a tangible non-transitorycomputer readable medium. The processor executable code, when executedby the processor, can cause the processor to generate a real-time viewfor viewing by the surgeon. The real-time view can include (i) amicroscope view of the eye and (ii) an augmented image having themicroscope view or a microscope image of the eye. The augmented imagecan further include an optical coherence tomography (OCT) image of atarget tissue region. The OCT image can be registered with themicroscope view or the microscope image. An actual target location maynot be visible in the microscope view or the microscope image. Theaugmented image can enable the surgeon to perceive information regardinga relative position of the distal end of the elongate probe with respectto the target location when the distal end of the elongate probe is notvisible in the microscope view or the microscope image. In some cases, agraphical visual element identifying a target location positioned in thetarget tissue region can be overlaid the microscope view or themicroscope image.

In yet another aspect, embodiments of the present invention encompass afiber-based apparatuses for performing a surgical procedure in a targettissue region disposed beyond a critical angle of an eye of a patient.Exemplary fiber-based apparatuses can include a sheath, and one or moreoptical fibers encapsulated by the sheath. The one or more opticalfibers can be configured to (i) transmit light energy sufficient tophotoablate the target tissue region, and (ii) enable optical coherencetomography (OCT) imaging of the eye. The fiber-based apparatus can beconfigured perform OCT imaging of the target tissue region along alongitudinal axis of the probe. In some cases, the target tissue regionincludes a trabecular meshwork, a juxtacanalicular trabecular meshwork,an inner wall of Schlemm's canal of the eye, and Schlemm's canal. Insome cases, the fiber-based apparatus configured to transmit the lightenergy sufficient to photoablate the target tissue region when an OCTscan indicates that a trabecular meshwork of the target tissue region issufficiently compressed. In some case, the fiber-based apparatus is ableto be configured to automatically stop transmission of light energy whenan OCT scan indicates that an inner wall of Schlemm's canal has beenpenetrated. In some cases, the fiber-based apparatus is configured toautomatically stop transmission of light energy when an OCT scanindicates that an inner wall of Schlemm's canal has been penetrated. Insome cases, the fiber-based apparatus is configured to notify thesurgeon to stop transmission of light energy when an OCT scan indicatesthat an inner wall of Schlemm's canal has been penetrated. In somecases, the fiber-based apparatus is configured to be detected by amicroscope-based OCT apparatus. In some cases, the fiber-based apparatusis configured to be detected by a microscope-based OCT apparatus andinformation processed by both the fiber-based apparatus and themicroscope-based OCT apparatus can be displayed so as to enable asurgeon to operate within the target tissue region.

In still another aspect, embodiments of the present invention encompassmicroscope-based optical coherence tomography (OCT) apparatuses for usein facilitating a surgical procedure in a target tissue region disposedbeyond a critical angle of an eye of a patient. Exemplarymicroscope-based OCT apparatuses may include an OCT unit configured to(i) detect a probe disposed in an anterior chamber of the eye, and (ii)enable OCT imaging of the eye. The microscope-based OCT is configured toperform OCT imaging of the target tissue region. In some cases, thetarget tissue region includes a trabecular meshwork, a juxtacanaliculartrabecular meshwork, an inner wall of Schlemm's canal of the eye, andSchlemm's canal. In some cases, the microscope-based OCT apparatus isconfigured to detect a fiber-based apparatus. In some cases, thefiber-based apparatus is configured to transmit the light energysufficient to photoablate the target tissue region when amicroscope-based OCT scan indicates that a trabecular meshwork of thetarget tissue region is sufficiently compressed. In some cases, thefiber-based apparatus is able to be configured to automatically stoptransmission of light energy when a microscope-based OCT scan indicatesthat an inner wall of Schlemm's canal has been penetrated. In somecases, the fiber-based apparatus is configured to automatically stoptransmission of light energy when a microscope-based OCT scan indicatesthat an inner wall of Schlemm's canal has been penetrated. In somecases, the fiber-based apparatus is configured to notify the surgeon tostop transmission of light energy when a microscope-based OCT scanindicates that an inner wall of Schlemm's canal has been penetrated. Insome cases, the fiber-based apparatus is configured to be detected bythe microscope-based OCT apparatus and information processed by both thefiber-based apparatus and the microscope-based OCT apparatus can bedisplayed so as to enable a surgeon to operate within the target tissueregion.

In still another aspect, embodiments of the present invention encompasscomputer program products for controlling a microscope-based opticalcoherence tomography (OCT) apparatus and a fiber-based apparatus duringa surgical procedure. The surgical procedure can be performed by asurgeon in a target tissue region disposed beyond a critical angle of aneye of a patient. Exemplary computer program products may includecomputer-executable code for instructing the microscope-based OCTapparatus to performing OCT imaging of the target tissue region, andcomputer-executable code for instructing the fiber-based apparatus toperforming OCT imaging of the target tissue region along a longitudinalaxis of a probe controlled by the surgeon. In some cases, the targettissue region includes a trabecular meshwork, a juxtacanaliculartrabecular meshwork, an inner wall of Schlemm's canal of the eye, andSchlemm's canal. In some cases, a computer program product can furtherinclude computer-executable code for instructing the fiber-basedapparatus to transmit light energy sufficient to photoablate the targettissue region when an OCT scan performed by the fiber-based apparatusindicates that a trabecular meshwork of the target tissue region issufficiently compressed. In some cases, a computer program product canfurther include computer-executable code for instructing themicroscope-based OCT apparatus to enable the fiber-based apparatus totransmit light energy sufficient to photoablate the target tissue regionwhen an OCT scan performed by the microscope-based OCT apparatusindicates that a trabecular meshwork of the target tissue region issufficiently compressed. In some cases, a computer program product canfurther include computer-executable code for instructing the fiber-basedapparatus combined with the microscope based OCT apparatus to enable thefiber-based apparatus to transmit light energy sufficient to photoablatethe target tissue region when an OCT scan performed by the fiber-basedapparatus combined with the microscope-based OCT apparatus indicatesthat a trabecular meshwork of the target tissue region is sufficientlycompressed. In some cases, a computer program product can furtherinclude computer-executable code for automatically stopping transmissionof light energy when an OCT scan performed by the fiber-based apparatusindicates that an inner wall of Schlemm's canal has been penetrated. Insome cases, a computer program product can further includecomputer-executable code for automatically stopping transmission oflight energy when an OCT scan performed by the microscope-based OCTapparatus indicates that an inner wall of Schlemm's canal has beenpenetrated. In some cases, a computer program product can furtherinclude computer-executable code for automatically stopping transmissionof light energy when an OCT scan performed by the fiber-based apparatuscombined with the microscope based OCT apparatus indicates that an innerwall of Schlemm's canal has been penetrated. In some cases, a computerprogram product can further include computer-executable code fornotifying the surgeon to stop transmission of light energy when an OCTscan performed by the fiber-based apparatus indicates that an inner wallof Schlemm's canal has been penetrated. In some cases, a computerprogram product can further include computer-executable code fornotifying the surgeon to stop transmission of light energy when an OCTscan performed by the microscope-based OCT apparatus indicates that aninner wall of Schlemm's canal has been penetrated. In some cases, acomputer program product can further include computer-executable codefor notifying the surgeon to stop transmission of light energy when anOCT scan performed by the fiber-based apparatus combined with themicroscope based OCT apparatus indicates that an inner wall of Schlemm'scanal has been penetrated. In some cases, a computer program product canfurther include computer-executable code for instructing themicroscope-based OCT apparatus to detect the fiber-based apparatus. Insome cases, the fiber-based apparatus can be configured to be detectedby a microscope-based OCT apparatus and information processed by boththe fiber-based apparatus and the microscope-based OCT apparatus can bedisplayed so as to enable a surgeon to operate within the target tissueregion.

In another aspect, embodiments of the present invention encompasstreatment methods that include viewing an augmented image on a viewingdevice, where the augmented image has a microscope view or a microscopeimage of the eye, and where the augmented image further has an opticalcoherence tomography (OCT) image of a target tissue region. The OCTimage can be registered with the microscope view or the microscopeimage. The OCT image can enable identification of a target locationpositioned in the target tissue region, and the target location may notbe visible in the microscope view or the microscope image. Relatedmethods may include advancing a distal end of an elongate probe withinan anterior chamber of the eye toward the target tissue region whileviewing the microscope view or the augmented image on the viewingdevice, where the distal end of the elongate probe is initially visiblein the microscope view or the microscope image and thereafter becomesnot visible in the microscope view or the microscope image due to totalinternal reflection in the eye. Related methods may further includeperforming the surgical procedure at the target location using theelongate probe while the distal end of the elongate probe is not visiblein the microscope view or the microscope image, and while perceivinginformation from the augmented image regarding a relative position ofthe distal end of the elongate probe with respect to the targetlocation.

INCORPORATION BY REFERENCE

All publications, patents, patent applications, journal articles, books,technical references, and the like mentioned in this specification areherein incorporated by reference to the same extent as if eachindividual publication, patent, patent application, journal article,book, technical reference, or the like was specifically and individuallyindicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims A better understanding of the features andadvantages of the provided system and methods will be obtained byreference to the following detailed description that sets forthillustrative embodiments, in which the principles of the invention areutilized, and the accompanying drawings of which:

FIG. 1 is schematic sectional view of an eye illustrating anatomicalstructures;

FIG. 2 is a perspective fragmentary view of the anatomy adjacent to theanterior chamber of an eye depicting the corneo-scleral angle and flowof aqueous fluid;

FIG. 3 is schematic sectional view of an eye illustrating a fiber-opticprobe crossing the anterior chamber from a corneal limbal paracentesissite toward the trabecular meshwork in the anterior chamber of the eye;

FIG. 4 and FIG. 5 schematically illustrate a system for aiding aphysician to perform a surgical procedure on an eye, in accordance withembodiments of the invention;

FIG. 6 illustrates both real images of the eye and fiber-optic probe andan exemplary augmented (virtual) image and augmented (virtual) view;

FIG. 6A depicts aspects of a patient eye and an optical device,according to embodiments of the present invention.

FIGS. 6B-C illustrate aspects of an augmented view or image, accordingto embodiments of the present invention.

FIGS. 7A-7F shows exemplary real and augmented/virtual images as viewedby a surgeon or user during a procedure;

FIG. 8 shows an exemplary system based on fiberoptic-based OCT, inaccordance with embodiments of the invention;

FIG. 9 shows exemplary augmented (virtual) images and augmented(virtual) view obtained using the system in FIG. 8;

FIG. 10 shows an exemplary system based on microscope-based OCT, inaccordance with embodiments of the invention;

FIG. 11 schematically illustrates an example of the OCT guidance system1100, in accordance with embodiments of the invention;

FIGS. 12A-D show examples of instruments that can be used in combinationwith the provided system;

FIG. 13 shows a flowchart of a method for determining a target locationand probe location, in accordance with embodiments;

FIGS. 13A-B depict aspects of treatment methods and aiding methods,respectively, according to embodiments of the present invention.

FIG. 14 shows an analyzing and control system that can be configured toimplement any analyzing and control systems disclosed in the presentapplication; and

FIG. 15 shows examples of pre-operative OCT images, and augmentedpre-operative OCT images showing collector channels and targetlocations.

DETAILED DESCRIPTION OF THE INVENTION

In the following detailed description, reference is made to theaccompanying figures, which form a part hereof. In the figures, similarsymbols typically identify similar components, unless context dictatesotherwise. The illustrative embodiments described in the detaileddescription, figures, and claims are not meant to be limiting. Otherembodiments may be utilized, and other changes may be made, withoutdeparting from the scope of the subject matter presented herein. It willbe readily understood that the aspects of the present disclosure, asgenerally described herein, and illustrated in the figures, can bearranged, substituted, combined, separated, and designed in a widevariety of different configurations, all of which are explicitlycontemplated herein.

The methods and apparatuses are well suited for combination withmultiple alternative MIGS approaches to treating glaucoma, such asiStent®, iStent Inject, Cypass®, and others, for example. Althoughreference is made to treatment without a goniolens in some embodiments,the methods and apparatus disclosed herein are also well suited forcombination uses with goniolenses.

Methods and systems disclosed herein can allow a larger cohort ofophthalmic surgeons to successfully perform MIGS procedures. Forexample, the disclosed methods and apparatus can allow for surgeries tomore uniformly and consistently create openings to enable improvedoutflow of aqueous fluid from the eye's anterior chamber into Schlemm'scanal, for example. In addition, the disclosed system and methods canlead to improved surgical outcomes, by allowing surgeons to identifytarget locations for openings into Schlemm's canal intended to increaseoutflow. In some cases, a target location may include a surface or layerof a tissue, or a position at a tissue, for example of the trabecularmeshwork, the juxtacanalicular trabecular meshwork (JCTM), the innerwall of the Schlemm's canal, the outer wall of the Schlemm's canal, thesclera, or desired combinations thereof.

The presently disclosed methods and apparatus may include thecombination of a surgical microscope image with sensing devices whichenable real-time heads-up display images to be concurrently viewed bythe surgeon. These real-time images can allow the surgeon to target andtreat locations within an eye which may not be readily visualized usingthe operating microscope alone, such as structures including thetrabecular meshwork and Schlemm's canal. The methods and apparatusdisclosed herein can allow a surgeon to view angle structures that areobscured or blocked by total internal reflection. For example, thedisclosed methods and apparatus can allow images or information of thoseotherwise poorly visible or non-visible structures, such as thecollector channel system, to be collected using OCT optical coherencetomography (OCT) technologies. A surgeon can concurrently view a realimage of the eye with an overlying projected image of ocular structuresby the placement of an image of those structures, such as the collectorchannel system via, for example, an OCT image of the collector channelsystem obtained earlier which is registered to visible markers, toenable the surgeon to identify and target preferred surgical sites. Inthis manner, the images viewed by the surgeon include real (optical) andprojected (virtual) images combined to enhance surgical targeting.Additional information can also be provided to the surgeon/viewer, suchas virtual images of otherwise non-visible structures and one or moresymbols to indicate both distances and movement, such as from a probetip to trabecular meshwork to Schlemm's canal. In some embodiments, OCTimaging can be used to identify collector channels of the eye, andenable the surgeon to identify sites by these target locations (e.g. byusing a graphical visual element such as a treatment reference marker toidentify a target location) displayed to the user to assist in thecreation of openings at appropriate locations in eye's trabecularmeshwork to increase flow. Embodiments of the present inventionencompass any of a variety of OCT scanning modalities or map, includingpre-operative and/or intra-operative OCT maps or images of the outflowsystem (e.g. Schlemm's canal and collector channels) such as thosedepicted in FIG. 15, which can be overlaid onto a microscope image orview. In some cases, one or more OCT images can be used to generate avirtual image of the angle structures, for example as shown in image 610of FIG. 6. In some cases, one or more OCT images can be used to generatea graphic depiction of the relationships of various structures and thesurgical instrument (e.g. fiber/probe), for example as shown in feature620 of FIG. 6.

Such displays can be coupled to the operating microscope in order topresent monocular or binocular virtual images from a display which isvisually combined with binocular real optical images of the eye, forexample. The methods and apparatus disclosed herein are well suited forutilization with ELT surgery and with implant device surgeries whichprovide openings to drain fluid from the eye. However, the providedsystem and methods can also be applied to various other surgicalprocedures where fiberoptic-based OCT may be utilized, e.g. any and allsurgeries using an endoscope.

Although specific reference is made to the treatment of glaucoma usingexcimer laser trabeculostomy (ELT), the methods and systems disclosedherein can be used with many other types of surgeries. For example, theembodiments disclosed herein can be used with other surgical procedures,including endoscopic procedures relating to orthopedic, neurosurgical,neurologic, ear nose and throat (ENT), abdominal, thoracic,cardiovascular, endocardiac, and other applications. The presentlydisclosed methods and apparatus can utilize OCT to improve targetingaccuracy and provide virtual visualization for enabling surgeons toperform procedures in regions that may not be readily visualized eithermicroscopically or endoscopically. Such applications include anyendoscopic procedure in which virtual visualization is augmented to realimages to assist surgical accuracy in 3-dimensional space, one exampleof which is an endovascular procedure in which the vessel curves orbends. Certain aspects may also be used to treat and modify other organssuch as brain, heart, lungs, intestines, skin, kidney, liver, pancreas,stomach, uterus, ovaries, testicles, bladder, ear, nose, mouth, softtissues such as bone marrow, adipose tissue, muscle, glandular andmucosal tissue, spinal and nerve tissue, cartilage, hard biologicaltissues such as teeth, bone, as well as body lumens and passages such asthe sinuses, ureter, colon, esophagus, lung passages, blood vessels, andthroat. For example, the devices disclosed herein may be insertedthrough an existing body lumen, or inserted through an opening createdin body tissue.

Devices for performing glaucoma surgery are described in U.S. Pat. Nos.4,846,172 and 9,820,883, the entire contents of which are hereinincorporated by reference.

In order to appreciate the described embodiments, a brief overview ofthe anatomy of the eye E is provided. As schematically shown in FIG. 1,the outer layer of the eye includes a sclera 17. The cornea 15 is atransparent tissue which enables light to enter the eye. An anteriorchamber 7 is located between the cornea 15 and an iris 19. The anteriorchamber 7 contains a constantly flowing clear fluid called aqueous humor1. The crystalline lens 4 is supported and moved within the eye by fiberzonules, which are connected to the ciliary body 20. The iris 19attached circumferentially to the scleral spur includes a central pupil5. The diameter of the pupil 5 controls the amount of light passingthrough the lens 4 to the retina 8. A posterior chamber 2 is locatedbetween the iris 19 and the ciliary body 20.

As shown in FIG. 2, the anatomy of the eye further includes a trabecularmeshwork (TM) 9, a triangular band of spongy tissue within the eye thatlies anterior to the iris 19 insertion to the scleral spur. The mobiletrabecular meshwork varies in shape and is microscopic in size. It isgenerally triangular in cross-section, varying in thickness from about100-200 μm. It is made up of different fibrous layers havingmicron-sized pores forming fluid pathways for the egress of aqueoushumor from the anterior chamber. The trabecular meshwork 9 has beenmeasured to about a thickness of about 100 μm at its anterior edge,Schwalbe's line 18, at the approximate juncture of the cornea 15 andsclera 17.

The trabecular meshwork widens to about 200 μm at its base where it andiris 19 attach to the scleral spur. The height of the trabecularmeshwork can be about 400 μm. The passageways through the pores intrabecular meshwork 9 lead through a very thin, porous tissue called thejuxtacanalicular trabecular meshwork 13, which in turn abuts theinterior wall of a vascular structure, Schlemm's canal 11. The height ofSchlemm's canal can be about 200 μm, or about half the height of thetrabecular meshwork. Schlemm's canal (SC) 11 is filled with a mixture ofaqueous humor and blood components, and connects to a series ofcollector channels (CCs) 12 that drain the aqueous humor into the venoussystem. Because aqueous humor 1 is constantly produced by the ciliarybody, and flows through the pupil into the anterior chamber from whichit passes through pores in the TM and JCTM into the SC and aqueousveins, any obstruction in the trabecular meshwork, the juxtacanaliculartrabecular meshwork, or Schlemm's canal, prevents the aqueous humor fromreadily escaping from the anterior eye chamber. As the eye isessentially a closed globe, this results in an elevation of intraocularpressure within the eye. Increased intraocular pressure can lead todamage of the retina and optic nerve, and thereby cause eventualblindness.

The obstruction of the aqueous humor outflow, which occurs in most openangle glaucoma (i.e., glaucoma characterized by gonioscopically readilyvisible trabecular meshwork), is typically localized to the region ofthe juxtacanalicular trabecular meshwork (JCTM) 13, located between thetrabecular meshwork 9 and Schlemm's canal 11, and, more specifically,the inner wall of Schlemm's canal.

When an obstruction develops, for example, at the juxtacanaliculartrabecular meshwork 13, intraocular pressure gradually increases overtime. Therefore, a goal of current glaucoma treatment methods is toprevent optic nerve damage by lowering or delaying the progressiveelevation of intraocular pressure. Many have searched for an effectivemethod of lowering and controlling intraocular pressure. In general,various pharmaceutical treatments have been employed to controlintraocular pressure. While these treatments can be effective for aperiod of time, the intraocular pressure often continues to increase inmany patients. However, patients often fail to follow prescribedtreatment regimens. As a result, inadequately controlled glaucoma leadsto an increased risk of irreversible damage to the optic nerve, andultimately, vision loss.

FIG. 3 is a side sectional view of the interior anatomy of a human eye Eshowing fiber-optic probe 23 in relation to an embodiment of a method oftreating glaucoma. After applying topical, peribulbar and/or retrobularanesthesia, a small self-sealing paracentesis incision 14 is created inthe cornea 15. The anterior chamber is stabilized with either a chambermaintainer using liquid flows or a viscoelastic agent. Fiber-optic probe23 can then be positioned and advanced through the incision 14 into theanterior chamber 7 until a distal end of the fiber-optic probe 23contacts and slightly compresses the desired target TM tissues.

Photoablative laser energy produced by laser unit 31 (shown in FIG. 4)is delivered from the distal end of fiber-optic probe 23 in contact tothe tissue to be ablated. The tissue to be ablated may include thetrabecular meshwork 9, the juxtacanalicular trabecular meshwork 13 andan inner wall of Schlemm's canal 11. An aperture in the proximal innerwall of Schlemm's canal 11 is created in a manner which does notperforate the distal outer wall of Schlemm's canal. In some embodiments,additional apertures are created in the target tissues. Thus, theresultant aperture or apertures are effective to restore relativelynormal rates of drainage of aqueous humor.

The fiber-optic probe 23 may comprise an optical fiber or a plurality ofoptical fibers encapsulated by an encapsulating sheath. The diameter ofa single optical fiber should be sufficiently large to transmitsufficient light energy to effectively result in photoablation of targettissues and in some embodiments to enable OCT imaging of the targettissues. In some embodiments, the optical fiber diameter is in a rangefrom about 4-6 μm. A single optical fiber or a plurality of opticalfibers can be used in a bundle of a diameter ranging from about 100 μmto about 1000 μm, for example. Core and sheaths can be encased within anouter metal sleeve, or shield. In some embodiments the sleeve isfashioned from stainless steel. In some embodiments, the outer diameterof sleeve is less than about 100 μm. In some embodiments, the diametercan be as small as 100 μm, as where smaller optical fibers areimplemented with laser delivery system. In some cases, the optical fibermay have a diameter of about 200 μm and the fiber-optic probe 23 mayhave a greater diameter such as 500 μm to encapsulate one or moreoptical fibers. In some embodiments, the sleeve can be flexible so thatit can be bent or angled.

FIG. 4 and FIG. 5 schematically illustrate a system 400 for aiding aphysician to perform a surgical procedure on an eye E, in accordancewith embodiments of the invention. The surgical operation procedure maycomprise inserting an elongate probe 23 from an opening into the eyeacross an anterior chamber to a target tissue region comprising atrabecular meshwork and a Schlemm's canal. In some embodiments, thesystem 400 may comprise an optical microscope 409 for the surgeon toview the eye during the procedure in real-time. Integrated within theoptical microscope 409 may be an optical coherence tomography (OCT)apparatus. The microscope may comprise a surgical operating microscope,for example. The system 400 may comprise an OCT unit 401 configured toperform an OCT scan of one or more target locations in the target tissueregion during the procedure. The OCT unit 401 as described herein maycomprise microscope OCT 403 or Fiber OCT 402, and combinations thereof,for example. Images captured by the OCT unit 403 or 402 may be processedby an image processing apparatus 412 of the controlling unit 410 togenerate a plurality of augmented images visualized by the physician inreal time. The augmented images can be shown on a display of the headsup display 407, and combined with optical images from the microscopewith an internal beam splitter to form monocular or binocular images asis known to one of ordinary skill in the art. As discussed elsewhereherein, a microscope view can include a “real” image, a “real” image andan overlaid virtual image, or an OCT image, for example. When amicroscope view includes an overlaid image, the overlaid image can beregistered with the “real” image using elements which enable suchalignment. According to some embodiments, a surgeon may first view asurgical instrument such as a probe a “real” image in the microscope ora video image from the microscope. In some cases, the surgeon may viewan augmented image or view. If there is an OCT overlaid on the “real”image, the surgeon might view both the “real” image and concurrently theoverlaid OCT image. The augmented images may be presented to thephysician through an eyepiece (or eyepieces) or oculars of themicroscope and/or a display of the microscope, and in someconfigurations may be viewed on a monitor screen. This may be beneficialto allow a surgeon to maintain a stereoscopic view of an operative sitethrough the oculars of the microscope while simultaneously viewingsuperimposed or adjacent images or information concurrently eitherstereoscopically or monocularly, for example. OCT scanned real timeimages, thereby enabling the creation of 3D OCT images and/or OCT-basedreal time information can be superimposed to the live view of one orboth oculars. In some embodiments, the system and method provides areal-time view including real and virtual images from both outside andinside of the anterior chamber during these surgeries.

The optical microscope 409 may be optically coupled with an OCT unit401. The optical microscope 409 may comprise a binocular microscope suchas a stereo-microscope comprising imaging lens elements to image anobject onto an eyepiece(s) or ocular 408 and concurrently to a camera405. The camera 405 is configured to capture optical images 505 of theeye. The optical images 505 may be transmitted to the controlling unit410 for processing. The camera 405 may comprise optical elements (e.g.,lens, mirrors, filters, etc). The camera may capture color images,greyscale image and the like.

The optical images 505 may be acquired at an appropriate image frameresolution. The image frame resolution may be defined by the number ofpixels in a frame. The image resolution can be smaller than or equal toabout 160×120 pixels, 320×240 pixels, 420×352 pixels, 480×320 pixels,720×480 pixels, 1280×720 pixels, 1440×1080 pixels, 1920×1080 pixels,2048×1080 pixels, 3840×2160 pixels, 4096×2160 pixels, 7680×4320 pixels,15360×8640 pixels or greater pixel frame, or within a range defined byany two combinations of the preceding pixel ranges. The imaging deviceor camera may have pixel size smaller than 1 micron, 2 microns, 3microns, 5 microns, 10 microns, 20 microns and the like. The camera 405may be, for example, a 4K or higher resolution color camera.

The captured optical images 505 may be a sequence of image framescaptured at a specific capture rate. In some embodiments, the sequenceof images may be captured at standard video frame rates such as about24p, 25p, 30p, 48p, 50p, 60p, 72p, 90p, 100p, 120p, 300p or higher, 50ior 60i. In some embodiments, the sequence of images may be captured at arate less than or equal to about one image every 0.0001 seconds, 0.0002seconds, 0.0005 seconds, 0.001 seconds, 0.002 seconds, 0.005 seconds,0.01 seconds, 0.02 seconds, 0.05 seconds. 0.1 seconds, 0.2 seconds, 0.5seconds, 1 second, 2 seconds, 5 seconds, or 10 seconds. In some cases,the capture rate may change depending on user input and/or externalconditions under the guidance of the control unit 410 (e.g. illuminationbrightness).

The optical images 505 may be captured in real time, such that imagesare produced with reduced latency, that is, with negligible delaybetween the acquisition of data and the rendering of the image. Realtime imaging allows a surgeon the perception of smooth motion flow thatis consistent with the surgeon's tactile movement of the surgicalinstruments (e.g. the elongate probe and the probe tip) during surgery.Real time imaging may include producing images at rates faster than 30frames per second (fps) to mimic natural vision with continuity ofmotion, and at twice that rate to avoid flicker (perception of variationin intensity). In many embodiments, the latency may comprise a timeinterval from light from the OCT system illuminating the eye untilinformation is shown to the user, and can no more than about 100 ms, forexample. In many instances, the latency comprises no more than one ortwo frames of the image shown on the display. For embodiments comprisingA-scan imaging from the distal end of the probe inserted into the eye,the latency can be less than an image frame rate, for example no morethan about 10 ms.

In some embodiments, the optical microscope 409 may be coupled to anelectronic display device 407. The electronic display 407 may be a headsup display device (HUD). The HUD may or may not be a component of themicroscope system 409. The HUD may be optically coupled into thefield-of-view (FOV) of one or both of the oculars. The display devicemay be configured to project augmented images 507 generated by thecontrolling unit 410 to a user or surgeon. The display device may becoupled to the microscope via one or more optical elements such asbeam-splitter or semi-reflection mirror 420 such that a physicianlooking into the eyepieces 408 can perceive in addition to the realimage augmented images represented and presented by the display device407. The display device may be visible through a single ocular to thesurgeon or user. Alternatively, the HUD may be visible through botheyepieces 408 and visible to the surgeon as a binocular image combinedwith the optical image formed with components of the microscope, forexample.

The display device or heads up display 407 is in communication with thecontrolling unit 410. The display device may project augmented imagesproduced by the controlling unit 410 in real-time to a user. Asdescribed herein, real time imaging may comprise capturing the imageswith no substantial latency, and allows a surgeon the perception ofsmooth motion flow that is consistent with the surgeon's tactilemovement of the surgical instruments during surgery. In some cases, thedisplay device 407 may receive one or more control signals from thecontrolling unit for adjusting one or more parameters of the displaysuch as brightness, magnification, alignment and the like. The imageviewed by a surgeon or user through the oculars or eyepieces 408 may bea direct optical view of the eye, images displayed on the display 407 ora combination of both. Therefore, adjusting a brightness of the imageson the HUD may affect the view of the surgeon through the oculars. Forinstance, processed information and markers shown on the display 407 canbe balanced with the microscope view of the object.

The heads up display 407 may be, for example, a liquid crystal display(LCD), a LED display, an organic light emitting diode (OLED), a scanninglaser display, a CRT, or the like as is known to one of ordinary skillin the art.

In some embodiments, the HUD 407 may comprise an external display. Forexample, the HUD may not be perceivable through the oculars in someembodiments. The HUD may be located in close proximity to the opticalmicroscope. The HUD may comprise a display screen, for example. The HUDmay comprise a light-emitting diode (LED) screen, OLED screen, liquidcrystal display (LCD) screen, plasma screen, or any other type ofscreen. The display device 407 may or may not be a touchscreen. Asurgeon may view real-time optical images of the surgical site and depthinformation provided by OCTs simultaneously from the HUD.

The OCT unit 401 may be coupled to the optical microscope 409. The OCTunit 401 may comprise a microscope OCT unit 403, a fiberoptic-based OCTunit 402 or a combination of both. The OCT unit 401 can comprise sweptsource OCT (SS-OCT), spectral domain OCT (SD-OCT), Fourier domain OCT(FD-OCT), or time domain OCT (TD-OCT), as known for OCT systems in theart. The OCT system may comprise a suitable resolution for viewingtissue structures of the eye such as Schlemm's canal and/or collectorchannels and may comprise a resolution within a range from less than 1to 10 microns, for example within a range from about 3 to 6 microns, forexample. The OCT unit 401 may comprise a low-coherence light sourcesuitable for producing OCT image information and interferometricinformation. The OCT unit 401 may produce OCT images with depthinformation and transmit the OCT images to the controlling unit 410. TheOCT unit may be at least partially controlled by the controlling unit.Control of the OCT unit by the controlling unit may include, forexample, activation of an OCT scan, parameters set-up, or customizablecontrol parameters.

The OCT unit may comprise a microscope OCT unit 403. The microscope OCTunit 403 may comprise a component of the optical microscope 409 or sharecomponents with the optical microscope. In some cases, the microscopeOCT unit 403 may comprise a stand-alone OCT unit adapted for such use.The microscope OCT unit may be positioned at a distance from the eyewithout contacting the eye. The microscope OCT unit may be operablycoupled to the optical microscope. The microscope OCT unit may utilizeone or more optical elements of the optical microscope such as theobjective lens. The microscope OCT unit 403 may be compatible with theoptical microscope system 409. For instance, the microscope OCT unit 403may be configured to allow for real-time adjustment of the OCT focalplane to maintain parfocality with the microscope view. In anotherinstance, the microscope OCT unit 403 may be capable of adapting tochanges in the optical power of one or more optical elements of theoptical microscope, such as the magnification of lenses such as theobjective lens or other lenses of the microscope. Microscope OCT unit403 may be configured to acquire OCT images using an engine (e.g., SDOCTengine) with a light source (e.g., NIR light source) and a detector(e.g., line-scan CCD). Depending on the different types of OCT,different spectrometers such as CCD or photodiode array detector may beused. The microscope OCT unit 403 may be configured to produce OCTimages as an A-scan, B-scan or C-scan depending on the scanningprinciples. For instance, by performing a fast Fourier transform (FFT),an axial scan (i.e., A-scan) as a function of depth can bereconstructed. By moving a mirror in x direction, a succession of A-scanlines is created, which can be stacked together to create a B-scan imageor two-dimensional image. By moving the mirror in both x-y directions, afull three-dimensional volume image or C-scan image (3D) can begenerated. The mirror can be coupled to any suitable actuator known toone of ordinary skill in the art, such as a galvanometer, a translationstage, a MEMs actuator or a piezoelectric crystal, for example. In someembodiments, the microscope OCT unit 403 may be activated to acquire Bmode images to provide information about a position of a probe relativeto a target location along the anterior and posterior plane of the eye.In some cases, the microscope OCT unit 403 may perform C-scan togenerate three-dimensional image of the target tissue region.

The OCT unit may comprise a fiberoptic-based OCT unit 402. According tosome embodiments, the terms “fiberoptic-based OCT unit” and “fiber-basedapparatus” may be used interchangeably. The fiberoptic-based OCT unit402 may comprise an optical fiber or an array of optical fibers todirect laser light pulses internal to the eye structure and to captureimages of the internal eye structures. The fiberoptic-based OCT unit mayperform OCT imaging while also delivering laser light pulses. Theoptical fiber can be inserted within the eye and in contact with tissueinside the eye. In some embodiments, the optical fiber can be the samefiber used in the fiber optical probe 23 to transmit laser light.Alternatively, the optical fiber may be a separate fiber such as astandard single mode or multi-mode optical fiber. The separate fiber maybe housed in the same fiber optic probe 23. For instance, the opticalfiber may be encapsulated in an encapsulating sheath of the probe 23that the encapsulating sheath is configured to stiffen the singleoptical fiber. This enables precise identification of a position of thetip of the probe 23 relative to Schlemm's canal, TM and the other targettissues. In some embodiments, a separate optical fiber for returning theback-scattered signal to the corresponding detector may be employed. Adichroic mirror 32 may be used to deflect the back-scattered signal tothe detector. In some embodiments, the optical fiber of the OCT unit andthe fiber-optic probe may be coaxial functioning as a coaxial endoscopefor identifying a position of the distal end of the probe relative totarget tissues. Alternatively, the optical fiber may be non-coaxial withthe fiber-optic probe. In some cases, a probe may include an array ofOCT detection fibers positioned around a treatment fiber.

The fiberoptic-based OCT unit 402 may be configured to generate axialscan images (A-Scan image). This may be beneficial to provide real timeinformation about the relative position of the distal end of the probewith respect to the target site or target location. The A-scan imagesmay be acquired at a high frequency such as in a range of 10 Hz to 5kHz. The A-scan images may be processed by the controlling unit 410 togenerate an image comprising a plurality of position or distance markerscorresponding to a plurality of positions of target tissues and theprobe tip. In some cases, a plurality of A-scan images may be averagedto generate an image for improved accuracy. The image from the A-scan(s)may be superimposed to the optical image to provide position informationof the fiber optical tip relative to target tissues along the axialdirection of the probe.

The system 400 may further comprise a user interface 413. The userinterface 413 may be configured to receive user input and outputinformation to a user. The user input may be related to control of asurgical tool such as the probe 23 operation. The user input may berelated to the operation of the optical microscope (e.g., microscopesettings, camera acquisition, etc). The user input may be related tovarious operations or settings about the OCT unit. For instance, theuser input may include a selection of a target location, a selection ofa treatment reference marker, displaying settings of an augmented image,customizable display preferences and the like. The user interface mayinclude a screen such as a touch screen and any other user interactiveexternal device such as handheld controller, mouse, joystick, keyboard,trackball, touchpad, button, verbal commands, gesture-recognition,attitude sensor, thermal sensor, touch-capacitive sensors, foot switch,or any other device.

In some embodiments, a microscope-based OCT 403 is used for guiding theprobe 23 and visualization. In some embodiments, a fiberoptic-based OCT402 is used for guiding the probe 23 and visualization. In someembodiments, both of the microscope-based OCT and fiberoptic-based OCTare employed in the system and used for guiding the probe 23 andvisualization. The microscope-based OCT and the fiberoptic-based OCT mayperform OCT scans along one or more planes of the eye. In some cases,when both of the OCTs are employed, the microscope-based OCT may beconfigured to perform a first OCT scan along an anterior-posterior planeof the eye and the fiberoptic-based OCT may be configured to perform asecond OCT scan along an axis transverse to the anterior-posteriorplane. In some cases, either of the microscope-based OCT andfiberoptic-based OCT may be used independently.

The microscope-based OCT and the fiberoptic-based OCT may or may notcomprise similar scan resolutions. In some cases, the microscope-basedOCT may perform a scan with higher scan resolution than thefiberoptic-based OCT. For instance, a B-scan performed by themicroscope-based OCT may have a higher resolution than an A-scanperformed by the fiberoptic-based OCT. Alternatively, a scan resolutionof the fiberoptic-based OCT may be higher than the microscope-based OCT.The axial resolution may be determined based on the bandwidth of thesource spectrum. The scan resolution may be determined to provide a fastenough frame rate to ensure real-time feedback. The resolution of eachof the OCT systems can be within ranges as described herein.

The microscope-based OCT and the fiberoptic-based OCT may or may nothave the same frame/scan rate. In some cases, the microscope-based OCTperforms B-scan and the fiberoptic-based OCT performs A-scan, and neednot require a volume scan of the surgical site. This can providereal-time position feedback at a higher rate. The frame rate of thecross-section view provided by the microscope-based OCT and the axialview provided by the fiberoptic-based OCT may be influenced by variousfactors such as the size of the scanning field, resolution or scanningrate. In some cases, the two-dimensional OCT images (B-scan) obtained bythe microscope-based OCT may be used to provide a coarse position of theprobe relative to a target tissue or target location, in which caserelatively high resolution and slow frame rate may be sufficient. Insome cases, the axial scan image (A-scan) obtained by thefiberoptic-based OCT may provide fine and precise position of the distalend of the probe relative to a small sized structure (e.g., SC, CC, TM),thus higher frame rate may be desired. In some cases, high frame ratemay be desired to minimize motion artifacts and enhance image quality.For instance, the axial scan of the fiberoptic-based OCT may have onedimensional A-scan frame/scan rate of at least 100 fps, or greater witha structural image resolution within a range from about 1 micron toabout 20 microns, for example. In many embodiments, the A-scan framerate is within a range from about 1 kHz to about 10 kHz. The OCT systemcan be configured to measure tissue while contacting the probe tip andup to a distance of at least about 10 mm from the probe tip, for exampleat least about 6 mm from the probe tip. These distances enable the probetip to target Schlemm's canal from a range of up to 6 mm in distancefrom the target site or target location. In some embodiments, the OCTapparatus may comprise a phase-based OCT configured to detect a motionof the distal end of the elongate probe, for example motion in a rangefrom about 20 nm to about 1 μm.

The system may provide surgeons augmented information overlaid to liveview of optical images of a surgical site. This is beneficial to reducedisruptions in surgical procedures by allowing surgeons to viewsupplemental information without moving their eyes away from themicroscope's viewing optics or a heads up display. The augmentedinformation may comprise a magnified field view of various areas of theeye on which they are operating. The augmented information may comprisedepth view comprising position information of the probe relative to atarget tissue. The augmented information may comprise a navigatedirection of an elongated probe. The augmented information may beprovided to a surgeon in substantially real-time. The augmentedinformation may comprise real time OCT images. The augmented informationmay comprise a plurality of visual graphical elements generated based onreal time OCT images and/or static OCT images. The terms “visualgraphical element” and “graphical visual element” may be usedinterchangeably throughout this application. The augmented informationmay comprise still and/or moving images and/or information (such astext, graphics, charts, plots, and the like) to be overlaid into anoperating microscope surgical viewing field or an optical microscopeimage displayed on a screen.

In some cases, the augmented information may be overlaid or superimposedto an optical image obtained by an optical microscope to form anaugmented image. The augmented image may be displayed on a screen eithersuch as the heads up display, a separate viewing monitor or both. Insome cases, the augmented information may be overlaid over directoptical path image such that the viewing field visible to a surgeonthrough the oculars of the microscope comprises both the optical pathimage and the overlaid augmented information. In some cases, theaugmented information may be superimposed to the optical image in apicture-in-picture format.

The controlling unit 410 may be configured to generate an augmentedlayer comprising the augmented information. The augmented layer may be asubstantially transparent image layer comprising one or more graphicalelements. The terms “graphical element” and “graphical visual element”may be used interchangeably throughout this application. The augmentedlayer may be superposed onto the optical view of the microscope, opticalimages or video stream, and/or displayed on the display device. Thetransparency of the augmented layer allows the optical image to beviewed by a user with graphical elements overlay on top of it. In someembodiments, the augmented layer may comprise real time OCT images orother information obtained by an OCT unit coupled to the opticalmicroscope.

As described above, the fusing of the optical microscopic image data andthe augmented information may comprise incorporating the augmentedinformation into the optical microscopic image. The augmented image datamay comprise one or more graphical elements associated with the depthinformation, target location and various other supplemental information.The graphical elements may be overlaid onto the optical microscopicimage with a beam splitter, for example. A graphical element can bedirectly overlaid onto an image of any object visible in the opticalmicroscopic image. A graphical element may also include any shape,boundary, or contour surrounding an image of any object in the opticalmicroscopic image. The object may be, for example, an instrumentinserted into the eye (e.g., probe), a portion of the probe, targettissues (e.g., SC, CC, TM, JCTM, sclera), and the like.

In some embodiments, the graphical elements may be configured todynamically change as a position or an orientation of the probe orinstrument changes relative to a target location. For example, agraphical element may indicate a location of a distal end of the probeshown in the optical image, or relative location or spacing betweentissues such as inner wall of SC, TM and the like. The graphicalelements may be configured to dynamically show the change in spacingbetween the tissue walls or distance between the tip and a targetlocation substantially in or near real-time on the optical image, as therelative distance between the probe tip and a target location changes,and/or when the probe tip compresses on tissue (e.g., surface oftrabecular meshwork).

In some embodiments, the augmented information may comprise anorientation of the probe relative to the target location. The graphicalelements may indicate the orientation of the probe relative to thetarget location. The graphical elements may be configured to dynamicallyshow the orientation of the probe relative to the target locationsubstantially in or near real-time on the optical image, as theorientation between the probe and the target location changes. In someinstances, a graphical element may indicate an orientation or axiallocation of the elongated probe. To indicate orientation (e.g.,direction), the graphical element may be provided in the form of anarrow. The arrow may be configured to change dynamically based onmovement/advancing of the probe.

The augmented layer or at least some of the graphical elements can bemapped or matched to the optical image using object recognitiontechniques or pattern matching techniques, such as feature pointrecognition. A feature point can be a portion of an image (e.g., sclerallandmarks, collector channel patterns, iris landmarks, etc.) that isuniquely distinguishable from the remaining portions of the image and/orother feature points in the image. A feature point may be detected inportions of an image that are relatively stable under perturbations(e.g., when varying illumination and brightness of an image).

FIG. 6 illustrates an exemplary augmented image or augmented view 600.As described above, the augmented image 600 may be viewed binocularly bya user or surgeon through oculars of the microscope, and may bedisplayed on a heads up display, an external display device, or adisplay coupled to a user interface. The augmented image or view maycomprise an optical image 505 or an optical path view through theoculars of an optical microscope. The optical image 505 may comprise atop-down view of the eye. The optical image or optical view may showanterior of an eye. The optical image or optical view may further showan elongated probe 23. The augmented image or view 600 may comprise aplurality of graphical visual elements and one or more OCT imagesadjacent to or overlaid over the optical image, for example by opticallycoupling the display to the optical path of the microscope with a beamsplitter. The plurality of graphical visual elements may comprisedifferent shapes and/or colors corresponding to different objects suchthat different objects shown in the optical image can be easilydistinguished from one another.

The plurality of graphical visual elements may comprise one or moretreatment reference markers 601, 602, 603 mapped to the one or moretarget locations. As discussed elsewhere herein, treatment referencemarkers 601, 602, 603 may correspond to target locations which are notoptically visible to the surgeon in the optical image or optical pathview 505. According to some embodiments, target locations may be locatedab interno, and treatment of the target locations may involve an abinterno approach. In some cases, the one or more target locations may bedetermined or identified based on a preoperative OCT image. As discussedelsewhere herein, preoperative and/or intraoperative OCT images may beobtained using either ab interno approaches and/or ab externoapproaches. According to some embodiments, a treatment reference markeror target location can be selected based on a location in the targettissue region that would provide a significant increase in outflowfollowing the formation of a channel therethrough (e.g. channel passingthrough the trabecular meshwork, the juxtacanalicular trabecularmeshwork, and the inner wall of Schlemm's canal, thus providing fluidcommunication between the anterior chamber and Schlemm's canal). Such aselection can be based on an identification of certain regions incollector channel networks or fields that are more dense, or thatcontain larger vessels, or a larger distribution of vessels, or that areless obstructed, or that correspond to circumferential flow areasprovided by Schlemm's canal. During real time optical imaging, the oneor more treatment reference markers 601, 602, 603 may be superimposed tothe target locations by detecting a pattern of the target locationidentified from the preoperative OCT image (e.g., one or more specificcollector channels). In some cases, a user or surgeon may be prompted toselect a target location(s) or treatment reference marker(s) through theuser interface 413. In some cases, a user or surgeon may be prompted torank or order selected target locations for treatment. Hence, the useror surgeon can specify a desired sequence in which the target locationswill be treated during the surgical procedure. For example, the user orsurgeon can specify that treatment reference marker 601 corresponds to atarget location that will be treated first, that treatment referencemarker 602 corresponds to a target location that will be treated second,and that treatment reference marker 603 corresponds to a target locationthat will be treated third. As discussed elsewhere herein, for examplewith reference to FIG. 15, treatment reference markers can be selectedbased on locations (e.g. locations in a target tissue region) that havebeen determined to correspond to bigger collector channels, more densecollector channel networks or fields, and/or and greater outflow. Insome cases, the treatment reference markers can be selected in anautomated fashion. In some cases, the treatment reference markers can beselected manually. Systems can be configured to guide the surgeon todirect the laser fiber to each of the selected treatment referencemarkers, sequentially. In some cases, a plurality of treatment referencemarkers may be shown simultaneously such as in the beginning of aprocedure for a user to select a target location. In some cases, theplurality of treatment reference markers may be shown sequentially asthe surgical operation progresses.

The plurality of graphical visual elements may also comprise a probeline 604 coaxial with the elongate probe 23. The probe line 604 shows anorientation of the probe in relation to the one or more targetlocations. The plurality of graphical visual elements may also comprisea distal tip marker 605 overlapping with the distal end of the elongatedprobe. Both of the probe line and the distal tip marker may dynamicallychange locations with respect to the actual positions and orientation ofthe elongate probe shown in the optical image or view 505, as the probeis moved within the anterior chamber of the eye. Hence, for example, asurgeon can use microscope to see the probe 23 as it enters the anteriorchamber, and can watch the probe as it moves relative to the eye. An OCTdetection mechanism can detect the probe 23, and an automated system orprocessor can generate the probe line 604 in response to the detection.Similarly, the automated system or processor can generate the guidancearrow 612.

The plurality of graphical visual elements may further comprise one ormore guidance arrows or markers 612 extending from the distal tip marker605 towards the one or more treatment reference markers (e.g., marker601). The one or more guidance arrows 612 may be configured to guide thephysician in aligning the distal end of the elongate probe to pointtowards the one or more target locations during the procedure, or guidethe physician in advancing the elongate probe towards the one or moretarget locations during the procedure. As discussed elsewhere herein,the one or more target locations may not be optically visible to thesurgeon in the optical image or optical view 505. For example, upon aselection of a target location, a guidance arrow 612 may be generatedpointing from the distal end of the probe (or the distal tip marker 605)to the selected target location (or the corresponding treatmentreference marker) such that the physician may advance the probe parallelor coaxial to the guidance arrow. The one or more guidance arrows 612may point radially from within the anterior chamber in differentdirections toward the target tissue region comprising the trabecularmeshwork and the Schlemm's canal. As discussed elsewhere herein, theheight of Schlemm's canal may be about half the height of the trabecularmeshwork. In some cases, the one or more guidance arrows mayautomatically appear when the distal end of the probe is located at apredetermined distance away from the target location, for example whenthe distal end of the probe is located about 6 mm or less from thetarget location. Alternatively, the one or more guidance arrows mayappear in response to a user input indicating a target location selectedfrom the plurality of target locations.

The augmented layer may further comprise one or more OCT images overlaidto the optical image. The OCT image or OCT-based image may provide depthinformation or position of the probe relative to a target location in aplane extending in a direction transverse to the optical image plane,for example substantially perpendicular to the optical image plane. Insome embodiments, one or more magnified field views may be generatedbased on OCT images 610, 620. For example, the OCT-based image may bemagnified by at least two to five times as compared to the opticalimage. For instance, as illustrated in FIG. 6, a two-dimensional OCTimage 610 obtained by the microscope OCT is overlaid on the opticalimage 505. In some cases, the scan used to generate image 610 isperformed intraoperatively. The terms “microscope OCT” and“microscope-based OCT” may be used interchangeably throughout thisapplication. The two-dimensional OCT images 610-4, 610-5, 610-6, 610-7,and 610-8 as described elsewhere herein may comprise embodiments,variation, or examples of the two-dimensional OCT image 610 and maycomprise substantially similar characteristics. For example, one or moreof these images may be generated based on an intraoperative scan. Insome cases, the OCT image 610 may comprise a B-scan image. Alternativelyor in combination, the OCT image 610 may be a three-dimensional image(C-scan). In some cases, real time or substantially real-time OCT imagesmay be displayed overlying the optical image in a picture-within-pictureformat. Alternatively or in combination, information derived from theOCT image may be overlaid to the optical image. In some embodiments,when the distal end of the probe is within a predetermined distance tothe selected target location, a microscope-based OCT scan may beperformed to produce the two-dimensional OCT image 610. The microscopebased OCT scan may extend along a plane defined by the present targetlocation, e.g. the target location corresponding to treatment referencemarker 601, and an opening into the eye, e.g. a small incision into thecornea (paracentesis) as described herein.

The two-dimensional image 610 may comprise a B-scan OCT image and one ormore visual graphical elements. The B-scan OCT image may comprise adensity plot, for example. The horizontal axis may correspond to thedirection of transverse scanning and the vertical axis may correspond tothe scanning depth. A gray level can be plotted at a particular pixel onthe OCT image corresponding to the magnitude of the depth profile at aparticular depth and transverse scanning position. The B-scan OCT imagemay be post-processed by the image processing apparatus of thecontrolling unit 410 for image enhancement, image compression or thelike. In some cases, the two-dimensional image 610 may be generated byaveraging a plurality of B-scan OCT images such that the two-dimensionalimage may be updated at a lower rate than the acquisition frame rate ofthe B-scan OCT images. Alternatively, the two-dimensional image 610 maybe updated at the same frame rate as the acquisition frame rate of theB-scan OCT images.

The B-scan OCT image may be obtained along an OCT image plane along theelongate axis of the probe 23. The B-scan OCT image plane can be alignedwith the probe line 604 along an anterior-posterior plane of the eye.For instance, the probe axis may be determined by an analysis of theoptical image acquired with the video, and the microscope-based OCT iscontrolled to align the OCT image plane with the elongate axis of theprobe. The microscope OCT plane can be displayed to the user with a lineextending along the probe axis with the line being shown on the displayand optically coupled to the microscope image.

In some cases, the two-dimensional OCT scan (B-scan) may be performedautomatically in a region where the probe line intersects at least onetreatment reference markers. The OCT scan region may comprise theanterior-posterior plane of the eye along the probe elongate axis. TheOCT scan region may comprise a portion of the anterior-posterior planesuch as including a portion of the distal end of the probe and theregion in front of the probe. The OCT scan region may not comprise theentire length of the probe. In some cases, the two-dimensional OCT scanmay be performed automatically upon detecting that the probe line issubstantially aligned coaxially with the one or more guidance arrows andoriented towards the one or more treatment reference markers. In somecases, the two-dimensional OCT scan may be performed automatically upondetecting that the distal end of the elongate probe is at a predefineddistance from a target location. For example, the predefined distancecan be within a range from about 1 mm to 6 mm.

The two-dimensional OCT image 610 may further comprise a plurality ofgraphical visual elements overlaid onto OCT image. For instance, one ormore treatment reference markers 601-1 may be mapped to the targetlocation in the OCT image. As discussed elsewhere herein, an OCT imagemay or may not be overlaid with a graphical visual element. In somecases, a graphical visual element can be separate from an OCT image andnot overlying it. According to some embodiments, an OCT image may beoverlying a microscope image. For example, an OCT image can be overlyinga microscope image via a microscope, a display, or a microscope combinedwith a display. The plurality of graphical visual elements may alsocomprise a probe marker 611 indicating at least the position of theprobe tip with respect to the target location corresponding to treatmentreference marker 601-1 in the depth cross-section. This provides thephysician depth information, thus guiding the physician in adjusting theadvancing direction of the probe in the anterior-posterior plane of theeye (i.e., depth). In some embodiments, a guidance arrow 613 may also beoverlaid to the OCT image for guiding the probe movement towards thetarget location, for example whereby the surgeon can visualize probemarker 611 advancing along guidance arrow 613 toward treatment referencemarker 601-01. In some cases, probe marker 611 may indicate or identifythe orientation of an elongate axis of the probe, for example withrespect to the target location corresponding to treatment referencemarker 601-1. In some cases, the probe marker 611 can be coaxial withthe elongate axis of the probe.

In some cases, the two-dimensional OCT image 610 may provide informationabout another OCT scan. For instance, based on the relative positioninformation between the probe tip and a target tissue location, afiberoptic-based OCT scan may be activated and graphical elements may beoverlaid to the OCT image 610 indicating the scan range (e.g., arrows614 in FIG. 7C) of the fiberoptic-based OCT scan. The scan range may bein a range such as from 1 degree to 45 degrees. Alternatively, thefiberoptic-based OCT scan may comprise an A-scan.

The fiberoptic-based OCT scan can be performed by the fiberoptic-basedOCT unit 402 as described above. The fiberoptic-based OCT scan may beperformed along the probe line 605 along an axis of the eye. Thefiberoptic-based OCT unit 402 may be configured to automatically performthe OCT scan upon detecting that the distal end of the elongate probe isat a second predefined distance from the target location. The secondpredefined distance may be within a range, for example, from about 1 mmto about 6 mm. In some cases, the fiberoptic-based OCT scan may beperformed after the microscope-based OCT scan. In some cases, thefiberoptic-based OCT scan may be performed independent of themicroscope-based OCT scan. In an example, the fiberoptic-based OCT scanmay be activated when the probe line is detected to be aligned with theguidance arrow either in the x-y plane identified by the optical imageor in the cross-section plane identified by the microscope-OCT image, ora combination of both. Alternatively, the fiberoptic-based OCT scan maybe activated manually.

In some embodiments, an image 620 or other information based on thefiberoptic-based OCT scan may be generated and overlaid onto the opticalimage in a picture-within-picture like format. In some cases, the scanused to generate image 620 is performed intraoperatively. In someembodiments, the image 620 may be generated by the microscopic OCT. Theimage 620 may or may not comprise the fiberoptic-based OCT image. Theimage 620 may be positioned close to the tip of the probe. The image 620can be positioned in any location within the optical view or on theaugmented image. The OCT images 620-5, 620-6, 620-7, 620-8, 620-9,620-90, and 620-91 as described elsewhere herein (e.g. FIGS. 7D-F and 9)may comprise embodiments, variation, or examples of the OCT image 620and may comprise substantially similar characteristics. For example, oneor more of these images may be generated based on an intraoperativescan.

The image 620 may comprise a plurality of graphical visual elements 608,609-1, 609-2, 609-3, 609-4, 609-5 generated based on thefiberoptic-based OCT scan or microscope-based OCT scan. In someembodiments, the fiberoptic-based OCT scan is performed between a distalend of the elongate probe and a target location to generate an OCTA-scan of the target location comprising a portion of the trabecularmeshwork and the Schlemm's canal. The plurality of graphical visualelements may comprise one or more A-scan distance markers 608, 609-1,609-2, 609-3, 609-4, and 609-5. The A-scan distance markers may providea magnified distance view of the relative position between the probe tipand tissue structures. The A-scan distance markers enable the physicianto observe the distal end of the elongate probe when the distal end isno longer visible in the images collected by the optical microscopicapparatus, and also aid the physician in guiding the distal end of theelongate probe towards the target location and also guide the surgeonregarding applying compression to the trabecular meshwork. In somecases, the A-scan distance markers may be generated when the distal endof the elongate probe is no longer visible in the microscope image as aresult of the distal end of the elongate probe being obscured due tototal internal reflection of the corner near an iridocorneal angle ofthe eye.

The A-scan distance markers may comprise a plurality of graphical visualelements showing relative distances between one or more of a distal endof the elongate probe (identified by distance marker 608), surface ofthe trabecular meshwork (identified by 609-1), juxtacanaliculartrabecular meshwork (JCTM) (identified by distance marker 609-2), aninner wall of the Schlemm's canal (identified by distance marker 609-3),an outer wall of the Schlemm's canal (identified by distance marker609-4), or sclera (identified by distance marker 609-5). According tosome embodiments, the distance markers 609-2 and 609-3 may be so closetogether as to be indistinguishable, as the JCTM is a very thin membraneand is situated adjacent the inner wall of Schlemm's canal. In FIG. 6the graphical elements are shown as lines and circles, however any othershapes or colors can be used to mark the relative distances. Theplurality of lines may comprise different colors, patterns, orthicknesses. The plurality of lines may be visually distinguishable fromone another. The A-scan distance markers are overlaid onto themicroscope image of the eye. The microscope image shows a top-down viewof the eye, and the A-scan distance markers show a magnified axial viewof the target location. In some cases, the axial view of the targetlocation is magnified by at least two to five times.

As illustrated in FIG. 6, the plurality of graphical visual elements maycomprise a first line or distance marker 608 corresponding to the distalend of the elongate probe, a second line or distance marker 609-1corresponding to the surface of the trabecular meshwork, a third line ordistance marker 609-2 corresponding to the juxtacanalicular trabecularmeshwork (JCTM), a fourth line or distance marker 609-3 corresponding tothe inner wall of the Schlemm's canal, a fifth line or distance marker609-4 corresponding to the outer wall of the Schlemm's canal, and asixth line or distance marker 609-5 corresponding to the sclera, forexample. Any number of lines or markers may be generated depending onthe specific tissue structure. One or more of the graphical visualelements may move relative to each other to reflect the real-timerelative position of the corresponding objects. For instance, the firstline 608 may appear to move relative to each of the second through sixthlines as the distal end of the elongate probe advances towards thetarget location. The plurality of lines allows the physician to knowwhere the distal end of the elongate probe is located relative to thesurface of the trabecular meshwork, the JCTM, the inner wall of theSchlemm's canal, the outer wall of the Schlemm's canal, and the sclera.The plurality of lines allows the physician to advance the distal end ofthe elongate probe in a precise manner toward the target locationcomprising the trabecular meshwork and the inner wall of the Schlemm'scanal. In some cases, the plurality of lines allows the physician toadvance the distal end of the elongate probe to apply gentle compressionon the trabecular meshwork, thereby avoiding over-compressing thetrabecular meshwork. In some case, compression of the trabecularmeshwork reduces the thickness of the trabecular meshwork to about 90microns, for example from an original thickness of approximately 150microns. In some cases, the plurality of lines allows the physician toknow whether the inner wall of the Schlemm's canal has been penetrated,and to avoid penetrating the outer wall of the Schlemm's canal. Forinstance, when the inner wall of the Schlemm's canal has beenpenetrated, the lines 609-2 and 609-3 may disappear from the augmentedimage indicating the probe tip has passed the inner wall of the SC (orthat the inner wall of SC has otherwise been penetrated), and in somecases, the physician may retract the elongate probe once the inner wallof the Schlemm's canal has been penetrated. The laser firing mayautomatically stop upon detection of penetration of the inner wall ofSchlemm's canal, for example. In some cases, when the inner wall of theSC is penetrated, a next target location may be shown in the images toinform the surgeon where to aim the probe next to create anotherablation channel in the inner wall of the Schlemm's canal, in the manneras described above. The target information may be generated from afiber-optic A-scan of the new target location. Additionally oroptionally, the target information may be generated from a microscopeB-scan of the new target location.

As noted above, penetration of the inner wall of Schlemm's canal can beindicated by disappearance of line 609-3, which is a graphical visualelement (e.g. A-scan distance marker) corresponding to the inner wall ofSchlemm's canal. In some cases, embodiments of the present invention areconfigured so that line 609-3 disappears from image 620 when the probetip penetrates the inner wall of Schlemm's canal. According to someembodiments, it can be assumed that the probe tip does not significantlymove once the trabecular meshwork is compressed and laser pulsesinitiated. In some cases, embodiments of the present invention areconfigured so that line 609-3 disappears from image 620 when laserpulses penetrate the inner wall of Schlemm's canal. In some cases,embodiments of the present invention are configured so that line 609-3disappears from image 620 when ablated tissue structures distal to theprobe tip are converted to gas and enter Schlemm's canal. According tosome embodiments, laser pulses can penetrate the inner wall of Schlemm'scanal, or the gas ablation product can enter Schlemm's canal, while theprobe tip does not penetrate into Schlemm's canal. According to someembodiments, an ablation channel can be created by ablation of thetrabecular meshwork, the juxtacanalicular trabecular meshwork, and theinner wall of Schlemm's canal, so as to form an aperture. Compression ofthe trabecular meshwork can be monitored by evaluating the distancebetween line 609-1 corresponding to the surface of the trabecularmeshwork and line 609-2 corresponding to the juxtacanalicular trabecularmeshwork (JCTM). According to some embodiments, penetration of the innerwall of Schlemm's canal can be monitored by evaluating the distancebetween distance markers, which can be A-scan distance markers, such asthe distance between line 609-3 and line 609-4. For example, as theinner wall of Schlemm's canal is penetrated and gas enters Schlemm'scanal, a localized and transient expansion of Schlemm's canal may occur(e.g. as a result of the incoming gas), and the distance between theinner and outer walls of Schlemm's canal may increase. At some timefollowing penetration, as Schlemm's canal is collapsed, the distancebetween the inner and outer walls of Schlemm's canal may decrease (e.g.from an initial distance of about 200 microns when the canal is expandedto a subsequent distance of about 20 microns when the canal iscollapsed.

As discussed elsewhere herein, total internal reflection within the eyeprevents a surgeon from viewing outflow structures that reside beyondthe “critical angle” of the anterior segment optical viewing pathway. Asshown in FIG. 6A, structures such as the central iris 619 a can beviewed by the surgeon using an optical device 640 a such as an opticalmicroscope, camera, video camera, or the like. This is because light 650a from the central iris 619 a exits the eye 680 a passing through thecornea 615 a and is received or detected by the optical device 640 a. Incontrast, structures in and near the iridocorneal angle 670 a, such asthe trabecular meshwork 672 a, are not visible when using the opticaldevice 640 a, subsequent to the total internal reflection due to thedome shape of the cornea. This is because light 660 a from theiridocorneal angle 670 a undergoes total internal reflection at theinterface between the eye's anterior surface structures, which includecornea and tear film 690 a and the air 695 a (or other material having adifferent refractive index that than of the anterior eye surface), andhence light from structures such as the trabecular meshwork 672 a doesnot exit the eye 680 a through the cornea and is not able to be receivedor detected by an optical device 640 a.

When performing certain minimally invasive glaucoma surgery (MIGS)procedures and other medical treatments, a surgeon will often move aninstrument such as a probe throughout various locations within theanterior chamber 607 a of the eye 680 a. When the instrument is locatedwithin the central or inner region of the anterior chamber 607 a (e.g.near the central iris 619 a and pupil 605 a) as indicated by the letterV, the instrument is optically visible to the surgeon both directly andvia a microscope. For example, the instrument may be seen in an opticalpath view or an optical path image provided by the optical device 640 a.In this sense, area V represents the area or space within the anteriorchamber which is optically visible to the surgeon, and for example canbe seen in an image provided by the optical device 640 a.

When the instrument (or a portion thereof, such as a distal tip) islocated toward the peripheral or outer region of the anterior chamber(e.g. peripheral to line 655 a, near the trabecular meshwork 672 a) asindicated by the letter N, the instrument (or portion thereof) is notoptically visible to the surgeon. For example, the instrument (orportion thereof) would not be able to be seen in a view or an imageprovided by the optical device 640 a. In this sense, area N representsthe region within the anterior chamber which is not optically visible tothe surgeon, and for example cannot be seen in a view or an imageprovided by the optical device 640 a.

Dashed line 655 a provides a representative illustration of the boundarythat separates the space V (visible) from the space N (not visible), andcorresponds to the “critical angle” discussed elsewhere herein.Relatedly, dashed line 656 a provides a representative illustration ofthe peripheral or outer boundary of space N.

Current methods to view structures which reside beyond the “criticalangle” require the use of devices called “goniolenses” which alter theoptical pathway by altering the optics of the curved corneal surface.There are two main categories of contact lenses used for this purpose:Those that allow a direct view into the iridocorneal angle 670 a andthose which allow an indirect e.g. reflected view using mirrors into theiridocorneal angle 670 a. The use of such devices to enable viewing ofthe iridocorneal angle structures requires skill sets to manipulatethese contact lenses in real time and to mentally invert the mirrorimages in the case of indirect goniolenses.

Advantageously, embodiments of the present invention provide systems andmethods that enable the surgeon to effectively and accurately move andposition a surgical instrument or probe, such as an excimer lasertrabeculotomy (ELT) device, throughout various desired or targetlocations in the peripheral anterior chamber (e.g. throughout region N),the view or image of which would otherwise be obscured or blocked due tototal internal reflection. What is more, embodiments of the presentinvention also enable the surgeon to effectively and accurately move andposition a surgical instrument or probe, such as a laser trabeculotomy(ELT) device, throughout various desired or target locations that arelocated peripheral to space N (e.g. through the trabecular meshwork 672a and the inner wall 625 a of Schlemm's canal 611 a).

For example, according to embodiments of the present invention, systemsand methods are detailed which provide the surgeon with an augmentedview or image of structure which could be visualized optically with agoniolens, but in this case are instead imaged without a goniolens (e.g.a tissue or tissue layer such as the trabecular meshwork 672 a) and, inaddition, may also include images of structure which could not bevisualized by a goniolens that includes an OCT image of a targetlocation at a target tissue region (e.g. a tissue or tissue layer suchas the juxtacanalicular trabecular meshwork, the inner wall of Schlemm'scanal, the outer wall of Schlemm's canal, and the sclera). Such imagemay be represented by graphic images similar to the structures if theycould be seen and also may be represented by, for example, graphicalvisual elements that identifies a target location and relative location.Relatedly, in some cases, a graphical visual element identifying atarget location can operate to identify a particular tissue or tissuelayer, such as the trabecular meshwork, the juxtacanalicular trabecularmeshwork, the inner wall of Schlemm's canal, the outer wall of Schlemm'scanal, or the sclera.

An augmented view or image can be generated by overlaying the OCT imageand the graphical element, and the graphical element can be registeredwith an optical path view or an optical path image. The augmented viewor image can also include a graphical element corresponding to theinstrument and/or a target location. For example, the augmented view orimage can include a probe marker that corresponds to the position of aprobe or a probe tip. In some cases, the augmented view or image caninclude a graphical element corresponding to a probe line or a guidancearrow. The graphical elements are particularly useful in providing thesurgeon with visible guiding cues for navigating space N and other areasor structures (e.g. sub-surface tissues or tissue layers disposedbeneath or peripheral to the trabecular meshwork 672 a such as the innerwall 625 a of Schlemm's canal 611 a) which are not optically visible.

In this way, the surgeon is presented with an augmented view or imagewherein a target location and/or an instrument (or portion thereof), ismade “visible” to the surgeon by virtue of one or more graphical visualelements alone or combined with one or more OCT images, wherein thetarget location and/or instrument (or portion thereof) is not visible inan optical view or an optical image without a goniolens. Hence, systemsand methods disclosed herein enable a surgeon to perform glaucomasurgery of the outflow structures (e.g. MIGS) without having to use agoniolens.

Panel (1) of FIG. 6A illustrates additional aspects of a critical anglefeature described herein. As shown here, light 650 a from a locationposterior to the cornea 615 a, having an angle of incidence “a” withrespect to a normal 675 a to the medium boundary 685 a (e.g. interfacebetween tear film 690 a and the air 695 a), crosses the boundary withpartial refraction. In contrast, light 660 a from a more peripherallocation within the anterior chamber 607 a, having an angle of incidence“b” with respect to the normal 675 a, does not cross the boundary 685 a,but instead is reflected back into the anterior chamber 607 a. Accordingto some embodiments, a critical angle “c” can be defined as thethreshold angle of incidence above which there is total internalreflection. Hence, it can be seen that with light 660 a, there is atotal internal reflection that prevents a surgeon from viewing certainoutflow structures that reside beyond the critical angle “c” of theanterior segment optical viewing pathway. According to some embodiments,the critical angle “c” is about 46 degrees, such that light, coming fromtissue structures or devices that are positioned within the anteriorchamber, which exceeds an angle of 46 degrees at the boundary 685 a isreflected back into the anterior chamber. In some cases, the value forthe critical angle can be determined based on an average value for apatient population. In some cases, the value for the critical angle canbe determined based on a specific value for a particular patient beingtreated. In some cases, the critical angle can correspond to a distanceof about between about 3 mm and about mm from the surface of thetrabecular meshwork.

FIG. 6B illustrates an exemplary augmented image or augmented view 600b. As described elsewhere herein, an augmented image may be viewed by auser or surgeon through oculars of a microscope for example with a headsup display adjacent to or overlying optically visible structures. Suchan augmented image can be displayed on a heads up display, an externaldisplay device, or a display coupled to a user interface. According tosome embodiments, augmented image 600 can be viewed on any of a varietyof viewing of viewing devices, such as a display device, a microscopedevice, a heads up display, a viewing monitor, a virtual reality viewingdevice, an augmented reality viewing device, or the like. As shown here,the augmented image or view 600 b can include an optical image 505 b oran optical path view through the oculars of an optical microscope, andoptical image 505 b includes an anterior or top-down view of an eye 607b having a sclera 17 b. The optical image or optical view also shows anelongated probe 23 b that has been inserted through a cornealparacentesis incision and into the anterior chamber of the eye.

The augmented image or view 600 b also includes an OCT image 610 b. Asshown here, OCT image 610 b corresponds to a side or cross-section viewof the eye. Further, augmented image or augmented view 600 b can includeanother OCT image 620 b. As shown here, image 620 b corresponds to ananterior or top-down view of the eye.

Dashed line 655 b provides a representative illustration of the boundarythat separates the space V within the anterior chamber which isoptically visible from the space N within the anterior chamber which isnot optically visible, and this boundary corresponds to the “criticalangle” visibility discussed elsewhere herein. Relatedly, dashed line 656b provides a representative illustration of the peripheral or outerboundary of space N within the anterior chamber.

Embodiments of the present invention provide systems and methods thatenable the surgeon to effectively and accurately move and position asurgical instrument, such as a probe, throughout various desired ortarget locations within the peripheral anterior chamber (e.g. throughoutspace N), the optical image or view of which would otherwise be blockeddue to total internal reflection, and to also navigate the surgicalinstrument to other areas or structures (e.g. sub-surface tissues ortissue layers disposed beneath or peripheral to the trabecular meshwork672 b) which are not optically visible. For example, as discussedelsewhere herein, OCT images 610 b and 620 b can include graphicalvisual elements that are disposed, or are at least partially disposed,peripheral to dashed line 655 b.

As shown here, OCT image 610 b includes a graphical visual element 611 bcorresponding to the elongate probe 23 b, which is disposed in space V,the space within the anterior chamber which is optically visible to thesurgeon. The portion of the iris posterior to the elongate probe may notbe visible in image 610 b (e.g. below graphical visual element 611 b)due to an OCT shadowing phenomena, whereby an object can cause opticalshadowing that obscures underlying tissues in an OCT image. Relatedly,OCT image 620 b includes a graphical visual element 608 b correspondingto a distal end 623 b of the elongate probe 23 b, which is similarlydisposed in space V. Dashed line 624 b represents the location of theprobe distal end 623 b.

As discussed elsewhere herein, for example with reference to FIG. 6C, asthe surgeon moves the distal end of the elongate probe from space V tospace N, the distal end of the probe 23 b will disappear from theoptical image or view 505 b, while OCT image 610 b allows the surgeon toseamlessly visualize the probe across this transition by virtue ofobserving graphical visual element 611 b as it moves from space V tospace N, and optionally into other areas or structures (e.g. sub-surfacetissues or tissue layers disposed beneath or peripheral to thetrabecular meshwork 672 b). Likewise, OCT image 620 b allows the surgeonto seamless visualize the probe across this transition by virtue ofobserving graphical visual element 608 b as it moves from space V tospace N, and optionally into other areas or structures (e.g. sub-surfacetissues or tissue layers disposed beneath or peripheral to thetrabecular meshwork). According to some embodiments, the boundary itself(i.e. dashed line 655 b) is described here for illustration purposesonly, and is not displayed anywhere in the augmented image or view 600b.

FIG. 6C illustrates an exemplary augmented image or augmented view 600c. The distal end (not shown) of the probe 23 c has now been advancedfrom space V (the positioning depicted in FIG. 6B) to space N, asindicated by dashed line 624 c of the optical view or image 505 c. Theaugmented image or view 600 c also includes an OCT image 610 c. As shownhere, OCT image 610 c corresponds to a side or cross-section view of theeye. The portion of the iris posterior to the elongate probe may not bevisible in image 610 c (e.g. below graphical visual element 611 c) dueto an OCT shadowing phenomena. Further, augmented image or augmentedview 600 c can include another OCT image 620 c. As shown here, image 620c corresponds to an anterior or top-down view of the eye 607 c.

Dashed line 655 c provides a representative illustration of the boundarythat separates the space V within the anterior chamber which isoptically visible from the space N within the anterior chamber which isnot optically visible, and this boundary corresponds to the “criticalangle” visibility discussed elsewhere herein. According to someembodiments, the boundary itself (i.e. dashed line 655 c) is describedhere for illustration purposes only, and is not displayed anywhere inthe augmented image or view 600 c. Relatedly, dashed line 656 c providesa representative illustration of the peripheral or outer boundary ofspace N within the anterior chamber.

OCT images 610 c and 620 c can include graphical visual elements thatare disposed, or are at least partially disposed, peripheral to dashedline 655 c. As shown here, OCT image 610 c includes a graphical visualelement 611 c corresponding to the elongate probe 23 c, which isdisposed in space V (the space within the anterior chamber which isoptically visible to the surgeon) and extends into space N (the spacewithin the anterior chamber which is not optically visible to thesurgeon). Relatedly, OCT image 620 c includes a graphical visual element608 c corresponding to a distal end of the elongate probe 23 c, which isdisposed in space N.

Because the surgeon has moved the distal end of the elongate probe 23 cfrom space V to space N, the distal end of the probe has disappearedfrom the optical image or view 505 c. During this movement, however, OCTimage 610 c allows the surgeon to seamlessly visualize the probe acrossthis transition from space V to space N, by virtue of observing thedistal portion 612 c of graphical visual element 611 c moving from spaceV to space N. Optionally, the surgeon may be guided by other graphicalvisual elements overlaid with OCT image 610 c, as discussed elsewhereherein, to move the probe throughout various locations in space N.During this guided navigational process, the surgeon can use OCT image610 c to visualize the position and/or location of probe 23 c relativeto anatomical structures of the eye 607 c by observing graphical visualelement 611 c (and optionally, distal portion 612 c) move relative tothe other graphical visual elements. For example, other graphical visualelements may correspond to sub-surface tissues or tissue layers disposedbeneath or peripheral to the trabecular meshwork 672 c.

Likewise, OCT image 620 c allows the surgeon to seamless visualizemovement of the probe across this transition from space V to space N, byvirtue of observing graphical visual element 608 c as it moves fromspace V to space N. Optionally, the surgeon may be guided by othergraphical visual elements overlaid with OCT image 620 c, as discussedelsewhere herein, to move the probe throughout various locations inspace N. During this guided navigational process, the surgeon can useOCT image 620 c to visualize the position and/or location of probe 23 crelative to anatomical structures of the eye 607 c by observinggraphical visual element 608 c move relative to the other graphicalvisual elements. For example, other graphical visual elements maycorrespond to sub-surface tissues or tissue layers disposed beneath orperipheral to the trabecular meshwork. In some cases, graphical visualelement 608 c may be generated when the distal end of the elongate probeis no longer visible in the microscope image as a result of the distalend of the elongate probe being obscured due to total internalreflection of the corner near an iridocorneal angle of the eye.

Hence, embodiments of the present invention are well suited for use inviewing and navigating in and around structures of the eye near theiridocorneal angle, such as the trabecular meshwork and Schlemm's canal,which would otherwise involve more difficult techniques, for exampletechniques requiring the use of a goniolens. Likewise, systems andmethods disclosed herein can allow a surgeon to view angle structuresthat are block by total internal reflection, by providing the surgeonwith images or information of those otherwise poorly visible ornon-visible structures, such as the collector channel system. Suchimages or information can be generated by making use of OCT opticalcoherence tomography (OCT) technologies.

FIGS. 7A-7F shows exemplary augmented images 700, 710, 720, 730, 740,750, 760, 770, 780, and 790 perceived by a physician or user during aprocedure. As illustrated in FIG. 7A (image 700), one or more treatmentreference markers 601, 602, 603 corresponding to one or more targetlocations may be overlaid over the optical image of an eye or an opticalpath view through the oculars of an optical microscope for a physicianto view and select. In the optical image or view shown here, it ispossible to visualize the anatomical structures of the eye within theanterior chamber, from the pupil to the trabecular meshwork. Asdiscussed elsewhere herein, however, the peripheral structures at ornear the iridocorneal angle, such as the trabecular meshwork, may not bevisible in the optical image or view. Hence, according to someembodiments, the optical image or view provided here is for illustrationpurpose only, and in practice will not include such peripheralstructures. The one or more target locations may be determined from apreoperative OCT image or other images then mapped to the live opticalimage as described elsewhere herein. Upon a selection of a targetlocation, a guidance arrow 612, (shown in image 710), extending from thedistal tip marker 605 towards the selected treatment reference marker601 corresponding to that selected target location may be generated toguide the physician, to orient the probe to longitudinally align withthe guidance arrow. In some cases, the treatment reference markers 602,603 corresponding to the non-selected target locations may disappearfrom the view after the first treatment reference marker 601 (orcorresponding target location) has been selected. Proceeding to FIG. 7B(image 720), the probe may be advanced towards the selected targetlocation corresponding to treatment reference marker 601 guided by theprobe line 604 coaxial with the elongate axis of the probe and theguidance arrow 612. When the probe tip is detected to be within apredetermined distance from the target location or when the probe lineis aligned with the guidance arrow as shown in FIG. 7C (image 730), anOCT scan may be performed. Relatedly, the OCT scan may be performed withthe probe tip is detected to be beyond the “critical angle” visibility,and consequently image 610-4 may be generated. As described elsewhereherein, the detection may be based on the live optical images. The OCTscan may be a microscope-based OCT scan and in some cases, atwo-dimensional image may be overlaid onto the optical image. In somecases, arrows 614 indicating a scanning range of the microscope-basedOCT may be overlaid to the optical image when a 3D scan (i.e., C-scan)is desired. The scanning range or volume may be defined by the twoarrows 614 pointing from the fiber tip to the target location.Alternatively, the microscope-based OCT may be 2-D scan (i.e., B-scan).The scanning plane may be along the longitudinal axis of the probe andthe anterior-posterior plane of the eye. The scanning range may be fromthe fiber optic tip to the target location as indicated by the arrow612. In some cases, the arrows 614 may indicate a scanning range forfiberoptic-based OCT. Similarly, the arrows 614 may define a scanningrange for a 3-D scan or 2-D scan of the fiberoptic-based OCT. Thescanning range may be in a range defined by an angle 714 such as from 1degree to 45 degrees.

As shown in image 740, the microscope-based OCT image 610-4 may compriseguidance arrows 613 to guide the physician in adjusting the probeorientation and advancing direction within an anterior-posterior planeof the eye. Alternatively, the guidance arrows may indicate a 3D OCTscan range. This OCT image supplements positional information that maynot be perceivable from the optical image. As described elsewhereherein, a probe marker 611 indicating at least the position of the probetip with respect to the target location corresponding to treatmentreference marker 601-1 may be overlaid onto the microscope-based OCTimage. As discussed elsewhere herein, the height of Schlemm's canal maybe about half the height of the trabecular meshwork. According to someembodiments, the guidance arrow 613 points in a direction towardSchlemm's canal. The location of treatment reference marker 601-1 cancorrespond to the position of Schlemm's canal.

As illustrated in FIG. 7D (image 750), as the distal tip marker 605corresponding to the distal end of the elongate probe approaches thetreatment reference marker 601 corresponding to the target location andis detected to be within a predetermined distance from the treatmentreference marker 601 (or where the distal end is detected to be within apredetermined distance from the target location), a second OCT scan maybe performed. The second OCT scan may be a fiberoptic-based OCT scanwhich can be used to generate image 620-5. In some cases, the second OCTscan may be a B-scan and arrows indicating a scan range may be overlaidto the optical image 610-5. Alternatively, the second OCT scan may be anA-scan along the axial of the probe and the scan range may not be shownon the augmented image. A magnified view of the second OCT scan (A-scanor image 620-5) may be overlaid onto the optical image in apicture-within-picture like format. For clarity, FIG. 7D shows amagnified view of an A-scan image 620-5 showing a plurality of A-scandistance markers, which may be overlaid on the augmented image. Aplurality of A-scan distance markers such as lines may be generatedbased on the A-scan result and overlaid to the optical image. Thedistance markers (e.g., fiberoptic tip position marker 608, TM distancemarker 609-1) may dynamically change locations or spacing to reflect therelative locations between the distal end of the probe and the surfaceof the trabecular meshwork, the JCTM, the inner wall of the Schlemm'scanal, the outer wall of the Schlemm's canal, or the sclera.

The accurate and precise positioning measurements of the probe tip andassociated markers can be used in combination with various ophthalmicsurgeries. In an example, ELT procedure may be performed under guidanceof the augmented images. The plurality of A-scan distance markers asshown in the example, may comprise a distance marker 608 correspondingto a distal end of the elongate probe or fiber optic tip, a distancemarker 609-1 corresponding to a surface of the trabecular meshwork, adistance marker 602-2 corresponding to a juxtacanalicular trabecularmeshwork (JCTM), a distance marker 609-3 corresponding to an inner wallof the Schlemm's canal, a distance marker 609-4 corresponding to anouter wall of the Schlemm's canal, or a distance marker 609-5corresponding to a sclera. The outer wall of Schlemm's canal may berelatively fixed with regard to the overall structure of the eye,whereas the inner wall of Schlemm's canal can move, along with thetrabecular meshwork, relative to the overall eye structure. Due tonormal physiological processes, the distance between the inner and outerwalls of Schlemm's canal can dynamically fluctuate, for example between20 microns (e.g. when filled with aqueous humor only) and 200 microns(e.g. when filled with aqueous humor and red blood cells). An ELT laserprobe can have an accuracy on the order of 1.7 microns per pulse, andthus can be operated to effectively ablate the inner wall of Schlemm'scanal without ablating the outer wall of Schlemm's canal. As discussedelsewhere herein, when the distance marker 609-3 corresponding to theinner wall of Schlemm's canal disappears due to penetration of the innerwall, a signal can be transmitted to the laser to cease delivery ofablation pulses, and a signal can be provided to the surgeon indicatingthat penetration has been completed. In this way, the system can providean automated stop signal, an informative stop signal, or both.

As illustrated in FIG. 7D (image 760), in OCT image 610-6, a real timeimage may show probe marker 611 moving toward the trabecular meshwork 9,as the microscope image shows distal tip marker 605 moving towardtreatment reference marker 601, and hence the surgeon can view thedisplayed movement of the probe as the probe tip advances toward thetarget. As shown in OCT image 620-6, when the probe tip advances towardthe target, the fiber optic tip distance marker 608 may move closer tothe distance markers corresponding to the target tissue region, whichmay include the trabecular meshwork and Schlemm's canal, as depicted bydistance marker 609-1 (corresponding to trabecular meshwork), 609-2(corresponding to juxtacanalicular trabecular meshwork), 609-3(corresponding to inner wall of Schlemm's canal), 609-4 (correspondingto outer wall of Schlemm's canal), and 609-5 (corresponding to sclera).For clarity, FIG. 7D shows a magnified view of an A-scan image 620-6showing a plurality of A-scan distance markers, which may be overlaid onthe augmented image.

As shown in FIG. 7E (augmented image 770), when the probe tip is incontact with the trabecular meshwork, the probe marker is in contactwith the trabecular meshwork as shown in OCT image 610-7, and distancemarker 609-1 may disappear from OCT image 620-7. When the probe tip isin contact with the trabecular meshwork, photoablation of the targettissue may be performed. The probe coupled to an energy source may beconfigured to deliver a plurality of pulses to the target location upondetecting that the distal end of the elongate probe is compressing theportion of the trabecular meshwork. As described herein, the pluralityof pulses is configured to produce an aperture through the trabecularmeshwork and into the Schlemm's canal by photoablation. For clarity,FIG. 7E shows a magnified view of an A-scan image 620-7 showing aplurality of A-scan distance markers, which may be overlaid on theaugmented image.

As shown in FIG. 7E (augmented image 780), the A-scan distance markersin OCT image 620-8 may indicate a penetration of the Schlemm's canalinner wall. For instance, when the inner wall of the Schlemm's canal hasbeen penetrated as shown in OCT image 610-8, the lines 609-2 and 609-3may disappear from the augmented image 780 indicating the probe tip haspassed the inner wall of the SC (or that the inner wall of Schlemm'scanal has otherwise been penetrated) and in some cases, physician mayretract the elongate probe once the inner wall of the Schlemm's canalhas been penetrated. According to some embodiments, a fiberoptic-basedOCT can be used to detect tissue structures within the target tissueregion, and can be used to detect when the inner wall of Schlemm's canalhas been ablated and penetrated. Relatedly, because the ablation processconverts the tissue into gas, detection of gas in Schlemm's canal (whichwas previously filled only with liquid, e.g. plasma or aqueous humor)can be used as another marker to identify when the inner wall ofSchlemm's canal has been penetrated. The laser firing may automaticallystop upon detection of penetration of the inner wall of Schlemm's canal,for example. Alternatively, in another example, the user may be notifiedby a processor to manually stop the laser firing. For clarity, FIG. 7Eshows a magnified view of an A-scan image 620-8 showing a plurality ofA-scan distance markers, which may be overlaid on the augmented image.

The controlling unit 410 may comprise a steering and control unit 414configured to automatically control the energy source to deliver theplurality of pulses upon detecting that the distal end of the elongateprobe is compressing the portion of the trabecular meshwork.Alternatively, the steering and control unit 414 may be configured togenerate an alert to the physician to manually control the energy sourceto deliver the plurality of pulses upon detecting that the distal end ofthe elongate probe is compressing the portion of the trabecularmeshwork. In some cases, the steering and control unit 414 may beconfigured to determine an amount by which the portion of the trabecularmeshwork is compressed by the distal end of the elongate probe based onthe A-scan distance markers. For instance, the amount of compression ofthe trabecular meshwork is determined based on a change in relativedistance between a first distance marker corresponding to the surface ofthe trabecular meshwork and a second distance marker corresponding tothe JCTM. In another instance, the steering and control unit 414 isconfigured to determine whether the portion of the trabecular meshworkis compressed to a predetermined thickness based on the A-scan distancemarkers. In some cases, the steering and control unit 414 may beconfigured to control an energy source to deliver a plurality of pulsesto cause photoablation of the portion of the trabecular meshwork and theinner wall of the Schlemm's Canal upon determining that the portion ofthe trabecular meshwork has been compressed to the predeterminedthickness

Referring back to FIG. 7E, the energy source may stop delivering theplurality of pulses to the target location upon detecting that the innerwall of the Schlemm's canal has been penetrated by the laser pulses. Theinner wall of the Schlemm's canal penetration may be indicated by thedisappearance of the line marker 609-3 corresponding to the inner wallof the Schlemm's canal. In some cases, the steering and control unit 414may be configured to detect whether the inner wall of the Schlemm'scanal has been penetrated by the photoablation of the portion of thetrabecular meshwork based in part on changes in relative distancesbetween the A-scan distance markers. In some cases, the steering andcontrol unit 414 is further configured to generate an alert to thephysician to retract the elongate probe away from the target locationupon detecting that the inner wall of the Schlemm's canal is penetrated.The alert may be in any form such as text, graphical visual elementsoverlaid over the optical image or audible alert.

As illustrated in FIG. 7F (image 790), the steering and control unit maybe further configured to generate an alert to the physician to locateanother treatment reference marker corresponding to the mapped locationof another target location of the eye upon successful completion of thecurrent operation. For example, when the inner wall of Schlemm's canalis detected to be penetrated and laser pulses are stopped, thesubsequent treatment reference marker 602 corresponding to the nexttarget location may appear and the surgeon can be guided to move to thenext treatment location as described elsewhere herein. Some or all ofthe previous described steps may be repeated for the subsequent targetlocations. For clarity, FIG. 7F shows a magnified view of an A-scanimage 620-9 showing a plurality of A-scan distance markers, which may beoverlaid on the augmented image.

FIG. 8 shows another example of the system 800, accordance withembodiments. The system 800 may be substantially the similar to thesystem 400 as described in FIG. 4, and may comprise one or morecomponents of system 400. The system 800 may utilize only afiberoptic-based OCT 402 to measure the eye E with OCT. The microscope409 may comprise the same optical microscope as described in FIG. 4. Inthis case, the OCT unit 401 may comprise only the fiberoptic-based OCT402, and the OCT unit may not share optical components of the microscope409. The A-scan information provided by the probe can be used todetermine a distance from the trabecular meshwork. The surgeon can usethe A-scan information provided on the display to align the probe withSchlemm's canal. For example, the A-scan information can be displayed tothe surgeon with an indication of the distance from Schlemm's canal, andan indication as to whether the distal end of the fiber optic probe isaligned with Schlemm's canal, for example.

FIG. 9 shows an exemplary augmented images or optical views 900 and 910shown to a user during a procedure using the system 800. The steps ofoverlaying guidance arrows, probe markers, probe tip markers 605,treatment reference markers to the optical image or view may be similarto those described in FIGS. 7A and 7B, in images 700, 710, and 720. Theorientation and advancing direction of the probe may be adjusted to suchthat the probe axial marker is aligned with the guidance arrow. Thealignment of the probe in the x-y plane may be achieved by using thetop-down view of the optical image of the eye. The position of the proberelative to the target location in the anterior-posterior plane may beestimated or calculated by a preoperative OCT image. When the probe tip(corresponding to distal tip marker 605) is detected to be within apredetermined distance from the target location (corresponding totreatment reference marker 601), a fiberoptic-based OCT scan may beperformed. The fiberoptic-based OCT scan may be an axial scan (i.e.,A-scan) or B-scan as described above. The fiberoptic-based OCT scan canbe the same as described elsewhere herein. A magnified view 620-90 ofthe OCT result may be overlaid onto the optical image. The OCT image 620may comprise a plurality of A-scan distance reference markers such as608, 609-1 as described previously. Alternatively, the OCT image maycomprise a two-dimensional OCT live image when a B-scan is performed.The OCT image 620-90 and 620-91 are useful to guide the physician inadvancing the tip in the axial direction, and provides information aboutthe relative position of the probe tip with respect to one or moretissues structures (e.g., trabecular meshwork 609-1). For example, asshown in image 910, as the tip is advanced, the distance marker 608 inthe OCT image 620-91 may move toward the other distance markers. Forclarity, FIG. 9 shows magnified views of A-scan images 620-90 and 620-91showing a plurality of A-scan distance markers, which may be overlaid onthe augmented image.

FIG. 10 shows another example of the system 1000, in accordance withembodiments of the invention. The system 1000 may utilize only amicroscope-based OCT unit 403. The OCT unit in the system 1000 maycomprise a microscope-based OCT. In this case, the OCT based augmentedinformation overlaid onto the optical image may be provided by the OCTscan performed by the microscope-based OCT unit 403. For instance, whenthe probe tip is detected to be within a predetermined distance from thetarget location, a microscope-based OCT scan may be performed. The scanplane may be along an anterior-posterior plane of the eye E and alongthe probe elongated axis as described elsewhere herein. The OCT scan maybe a high resolution scan. For example, a structural scan resolution maybe in a range from about 1 μm to about 5 μm. The scan may providepositional information of the probe tip relative to the target locationor tissue structures (e.g., trabecular meshwork, juxtacanaliculartrabecular meshwork (JCTM), an inner wall of the Schlemm's canal, anouter wall of the Schlemm's canal, or sclera). In some cases, a realtime OCT image with markers such as image 610 may be produced andoverlaid onto the optical image. In some cases, in addition to the image610, a magnified view of relative positions of the probe tip and thetissue structure such as image 620 may be generated based on themicroscope-based OCT and overlaid onto the optical image.

FIG. 11 schematically illustrates an example of the OCT guidance system1100, in accordance with embodiments of the invention. The system 1100may comprise the same components of the system 400 as described in FIG.4, except that the system 1100 may not comprise a separate laser unitfor the fiber optic probe. The system 1100 may be used for guiding anysurgical tools inserted internal to the eye E as described elsewhereherein. For instance, the system 1100 may provide guidance to locatestent location for implant. Examples of implant devices include theCyPass® microstent and the iStent®, which target the suprachoroidalspace and Schlemm's canal, respectively. In this case, the fiber opticfor the OCT scan may be co-axial with a surgical tool 1101 that may notcomprise the fiber optic for the ELT surgery.

FIGS. 12A-D show examples of instruments that can be used in combinationwith the provided system. The various instruments may not be coupled toa laser source. The device may comprise a substantially elongated shape.As illustrated in the anterior view of an eye depicted in FIG. 12A,augmented information may be overlaid onto the optical view or image 505of the eye and the instrument in a similar as described elsewhereherein. For instance, one or more treatment reference markers 601 and anarrow or probe line 604 co-axial to the instrument 24 may besuperimposed to the optical image. As shown here, the eye includes aniris 19, a trabecular meshwork 9, and a cornea 15. It is understood thatinstead of depicting the cornea 15, this image could also depict thesclera in substitution of the cornea. In an optical image or view 505shown here, it is possible to visualize the anatomical structures of theeye within the anterior chamber, from the inner pupil to theiridocorneal angle. As discussed elsewhere herein, however, theperipheral structures at or near the iridocorneal angle, such as thetrabecular meshwork 9, may not be visible in the optical image or view.Hence, according to some embodiments, the optical image or view providedhere is for illustration purpose only, and in practice will not includesuch peripheral structures.

A guidance arrow 612 may be displayed to guide the advancing directionand orientation of the instrument 24. In some cases, the fiber optic forOCT scan may be co-axial or enclosed in a housing of the instrument 24to provide a relative position of the distal end of the instrument withrespect to treatment location. In some cases, an elongate probe 24 maycomprise one or more stents 1220 a loaded thereon, and the stents 1220 amay be implanted in the trabecular meshwork 9 and configured to connectthe anterior chamber to the Schlemm's canal and create a permanentopening into Schlemm's canal. Embodiments of the system described hereincan be configured to aid a physician in advancing and implanting the oneor more stents 1220 a at target locations with aid of the graphicalvisual elements (e.g. treatment reference markers and arrows) registeredwith a real microscope image of the eye. For example, the disclosedsystem may be configured to aid the physician in advancing and sliding astent 1220 a sideways into Schlemm's canal and positioning the stentpermanently in Schlemm's canal with aid of the graphical visual elements(e.g. treatment reference marker 601, probe line 604, and/or guidancearrow 612) registered with the microscope image.

In some cases, the system may be configured to aid the physician inadvancing a plurality of stents along an elongate axis of the elongateprobe, injecting the plurality of stents into Schlemm's canal, andpositioning the plurality of stents permanently in Schlemm's canal, withaid of the graphical visual elements registered with the microscopeimage. For example, as depicted in FIG. 12B, Panel (1), an elongateprobe 1210 b includes a housing 1212 b and an insertion mechanism 1214b. As depicted in Panel (2), the insertion mechanism 1214 b can beloaded with a stent 1220 b, and the stent 1220 b can include a head 1222b, a thorax 1224 b, a flange 1226 b, and an outflow orifice 1228 b. FIG.12B, Panel (3) depicts two stents 1220 b which have been implanted intothe trabecular meshwork 9, as viewed from the anterior chamber. As shownhere, the flange 1226 b of each stent 1220 b includes an inlet orifice1227 b, which is in fluid communication with one or more outfloworifices (not shown). Because stents 1220 b do not extend significantlyfrom the trabecular meshwork 9 toward the central portion of theanterior chamber, the stents are not visible in a microscope image orview as a result of being obscured due to total internal reflection ofthe corner near the iridocorneal angle of the eye. OCT guidanceembodiments as disclosed elsewhere herein are well suited for assistingthe surgeon in delivering the stents (while loaded on the elongateprobe) to the trabecular meshwork 9. For example, OCT guidanceembodiments as discussed with reference to FIG. 6 can be used to helpguide the surgeon to implant a stent at a target location in thetrabecular meshwork. In some cases, the target location can correspondto the location of a collector channel, or be based on the distributionor density of multiple collector channels. With returning reference toFIG. 12B, as depicted in Panel (4), when a stent 1220 b is implanted inthe eye, the flange 1226 b resides in the anterior chamber 7, the thorax(not visible) resides in the trabecular meshwork 9, and the head 1222 bresides in Schlemm's canal 11. Because the inlet orifice is in fluidcommunication with the outflow orifices, aqueous humor can flow from theanterior chamber into Schlemm's canal.

As depicted in Panels (1)-(7) of FIG. 12C, in some cases, an elongateprobe 1210 c may comprise a micro-stent 1220 c loaded thereon, and themicro-stent 1220 c may be configured to create a permanent conduitbetween the anterior chamber 7 and a supraciliary space 27. In somecases, the stent 1220 c may include a sleeve 1221 c, such as a titaniumsleeve, an inlet 1222 c, a retention feature 1223 c, and an outlet 1224c. The system disclosed herein can be configured to aid the physician inadvancing the micro-stent 1220 c to the supraciliary space 27 with aidof the graphical visual elements registered with the microscope image.For example, the system can be configured to aid the physician inadvancing the micro-stent 1220 c to the supraciliary space 27 using areal time OCT image of the supraciliary space 27 generated by any of theOCT apparatus described elsewhere herein. The system can also beconfigured to aid the physician in positioning a proximal collar portionor sleeve 1221 c of the micro-stent 1220 c in an anterior chamber angle28 with aid of the graphical visual elements registered with themicroscope image. OCT guidance embodiments as disclosed elsewhere hereinare well suited for assisting the surgeon in delivering the stent (whileloaded on the elongate probe) to the anterior chamber angle. Forexample, OCT guidance embodiments as discussed with reference to FIG. 6can be used to help guide the surgeon to implant a stent at a targetlocation in the anterior chamber angle.

In some cases, as depicted in Panels (1)-(4) of FIG. 12D, an elongateprobe 1210 d may comprise a gel stent 1220 d configured forsubconjunctival filtration loaded thereon. As shown in Panel (1), aninjector or elongate probe 2120 d can be inserted through an incision inthe cornea 15, and advanced across the anterior chamber 7. As shown inPanel (2), the elongate probe can be further advanced into thesubconjunctival space 27. Panel (3) illustrates deployment of the distalportion of the gel stent 1220 d into the subconjunctival space. Panel(4) depicts gel stent 1220 d in the implanted position, where itfunctions to drain aqueous humor from the anterior chamber 7 into thesubconjunctival space 27. The gel stent 1220 d may be configured tocreate a channel through the sclera to allow flow of aqueous humor fromthe anterior chamber into a subconjunctival space. The system disclosedherein can be configured to aid the physician in positioning andimplanting the gel stent 1220 d with aid of the graphical visualelements registered with the microscope image. For example, OCT guidanceembodiments as disclosed elsewhere herein are well suited for assistingthe surgeon in delivering the stent (while loaded on the elongate probe)to the subconjunctival space. Relatedly, OCT guidance embodiments asdiscussed with reference to FIG. 6 can be used to help guide the surgeonto implant a stent at a target location in the subconjunctival space.

FIG. 13 shows a flowchart of a method 1300 for determining a targettreatment location and probe location, in accordance with embodiments.The method may use one or more of the systems described herein. In afirst step 1301, an anterior image of the eye may be obtained by acamera or video camera of an optical microscope. In a second step 1303,one or more target locations (or treatment reference markerscorresponding to the target locations) are overlaid or mapped over theoptical image or optical view to the user. The one or more targetlocations may be determined based on reference image data comprising anOCT image of the eye. The OCT image of the eye may be obtained using anOCT apparatus prior to the surgical procedure. In some cases, the OCTimage of the eye may comprise an image of an anterior segment of the eyecomprising a network of collector channels and one or more individualcollector channels in at least two quadrants from the OCT image may beidentified. The preoperative OCT image may have high resolution.

FIG. 15 shows examples of preoperative OCT images 1500, and augmentedpreoperative OCT images 1510 and 1520 showing collector channels andtarget locations. As shown in the examples, the preoperative OCT imagesmay be 3D images. One or more collector channels and/or target locationsmay be identified from the high resolution preoperative images. Asdiscussed elsewhere herein, the trabecular meshwork 9 is in fluidcommunication with a series or network of collector channels 12 (viaSchlemm's canal). OCT image 1500 depicts a location 9 a of thetrabecular meshwork 9 associated with subsurface tissue where the numberor density of collector channels 12 is relatively high. In contrast,location 9 b of the trabecular meshwork 9 is associated with subsurfacetissue where the number or density of collector channels 12 isrelatively low.

In some cases, augmented information such as guidance arrows 613 may beoverlaid onto the preoperative images. For example, preoperative OCTimage 1510 is overlaid with a guidance arrow 613 that can be used forguiding an elongate probe toward a target location. As depicted in FIG.15, preoperative OCT image 1510 can also be combined with a microscopeview or microscope image 1505, in which iris 19 and elongate probe 23can be seen.

As discussed elsewhere herein, a treatment reference marker cancorrespond to or can be mapped to a target location in an OCT image. Insome cases, one or more target locations can be identified or designatedin an OCT image. In some cases, the one or more target locations (e.g.621, 622) are located at positions corresponding to the one or moreindividual collector channels (or alternatively, positions correspondingto one or more regions containing dense networks or fields of collectorchannels) proximal to the trabecular meshwork and an inner wall of theSchlemm's canal. As shown here, treatment reference marker 601 can beoverlaid on the OCT image and/or on the microscope view or image attarget location 621, and treatment reference marker 602 can be overlaidon the OCT image and/or on the microscope view or image at targetlocation 622. In some cases, locations of the one or more individualcollector channels (or network regions) may be registered relative to atleast one distinguishable anatomical structure in the eye such as theiris. The plurality of target locations may be estimated manually by theuser or automatically by the processor. A user or physician may beallowed to select a target location through the user interface asdescribed elsewhere herein. According to some embodiments, the techniqueof identifying target locations and/or treatment reference markersdepicted in FIG. 15 can be used in conjunction with a subsequentgoniolens-facilitated treatment. According to some embodiments, thetechnique of identifying target locations and/or treatment referencemarkers depicted in FIG. 15 can be used in conjunction with other OCTguided techniques discussed herein with reference to, for example, FIG.6. As shown in FIG. 15, an OCT image can be used to identifying and/ortarget collector channels or networks of collector channels. Targetlocations can be selected based on where collector channels are largerand/or collector channel networks or fields are more dense (e.g. 4o'clock position), as opposed to where collector channels are smallerand/or collector channel networks are less dense (e.g. 2 o'clockposition). In some cases, a target location can be designated to atpositions in Schlemm's canal that are close to the collector channelsare larger, the collector channel networks or fields are more dense,and/or the collector channels, networks, or fields are the leastobstructed (e.g. that provide the highest volume of outflow). In somecases, target locations can be ranked or ordered based on these size,density, and/or obstruction or flow parameters. In some cases, OCTimages can be used to determine locations where flow in Schlemm's canalis circumferential and/or where flow is segmented, and target locationscan be selected so as to correspond to locations where flow iscircumferential. In some cases, a surgeon can use OCT images such asthose depicted in FIG. 15 to make a decision regarding where to positionor move a treatment probe or device, without requiring the assignment ofa target location or the overlaying of a graphical visual element. Forexample, the OCT image may show the collector channels, networks, and/orfields, and the surgeon may make the probe positioning or movementdecision based on such anatomical features. The OCT image can enable thesurgeon to identify a target location or desired treatment locationpositioned in the tissue without requiring that that target location ortreatment location be labeled or marked, for example with a graphicalvisual element or a treatment reference marker.

With returning reference to FIG. 13, in a third step 1305, one or moreguidance graphical elements may be superimposed to the optical imagesuch that the physician may adjust the advancing direction and/ororientation of the probe to move towards the selected target location inat least the optical image plane. In a fourth step 1307, when the probetip is detected to be within a predetermined distance from the targetlocation, a microscope-based OCT image may be obtained along thelongitudinal axis of the probe and the anterior-posterior plane of theeye. Next 1309, the microscope-based OCT image and associated markersmay be overlaid onto the optical image to guide the physician inadjusting the probe orientation and advancing direction in the OCT imageplane. In a sixth step 1311, a fiberoptic-based OCT scan may beperformed along the axis of the probe. The fiberoptic-based OCT scan maybe an A-scan or B-scan to provide relative position between the probetip and tissues when the probe tip is within a predetermined distancefrom the target location. The fiberoptic-based OCT image and/or distancemarkers generated based on the OCT image may be overlaid to the opticalimage 1313. In an eighth step 1315, the treatment may be displayed orviewed in real-time at the treatment locations in order to adjustmovement of the probe based at least in part on the augmentedinformation.

Although FIG. 13 shows a method in accordance with some embodiments aperson of ordinary skill in the art will recognize many adaptations forvariations. For example, the steps can be performed in any order. Someof the steps may be deleted, some of the steps repeated, and some of thesteps may comprise sub-steps of other steps. The method may also bemodified in accordance with other aspects of the disclosure as providedherein.

As shown in FIG. 13A, embodiments of the present invention encompassmethods for performing surgical procedures at a target location of aneye of a patient. An exemplary treatment method 1300 a includes viewinga real-time view on a viewing device, as illustrated by step 1310 a,advancing a distal end of an elongate probe within an anterior chamberof the eye toward the target tissue region while viewing the viewingdevice, as illustrated by step 1320 a, and performing the surgicalprocedure using the elongate probe while the distal end of the elongateprobe is not visible in a microscope view or a microscope image providedby the viewing device, and while perceiving information from amicroscope view or a microscope image regarding a relative position ofthe distal end of the elongate probe with respect to the targetlocation, as illustrated by step 1310 c. According to some embodiments,the target location is positioned in a target tissue region of an eye ofa patient. In some cases, the real-time view includes a microscope viewof the eye or an augmented image. The augmented image can include themicroscope view of the eye or a microscope image of the eye. Theaugmented image can further include an optical coherence tomography(OCT) image of the target tissue region. The OCT image can be registeredwith the microscope view or the microscope image. A graphical visualelement corresponding to the target location can be overlaid themicroscope view or the microscope image. The target location may not bevisible in the microscope view or the microscope image. According tosome embodiments, methods include advancing the distal end of theelongate probe within the anterior chamber of the eye toward the targettissue region while viewing the microscope view or the augmented imageon the viewing device. In some cases, the distal end of the elongateprobe is initially visible in the microscope view or the microscopeimage and thereafter becomes not visible in the microscope view or themicroscope image due to total internal reflection in a region of theeye. In some cases, this region of the eye includes the target tissueregion. In some cases, this region is beyond the “critical angle”visibility, as discussed elsewhere herein.

As shown in FIG. 13B, embodiments of the present invention encompassmethods of assisting a surgeon to perform a surgical procedure on an eyeof a patient. As shown here, method 1300 b includes providing areal-time view to the surgeon, as illustrated by step 1310 b. In somecases, the real-time view includes a microscope view of the eye 1320 b.In some cases, the real-time view includes an augmented image, such asaugmented image 1330 b or augmented image 1340 b. In some cases, anaugmented image 1330 b (version (A)) can include the microscope view ofthe eye 1320 b. In some cases, an augmented image 1340 b (version (B))can include a microscope image of the eye 1350 b. Either version of theaugmented image (i.e. augmented image 1330 b or augmented image 1340 b)can include an OCT image of a target tissue region of the eye 1360 b.The OCT image 1360 b can enable identification of a target location. Insome embodiments, a surgeon 1390 can view microscope view 1320 b, andthen view either augmented view 1330 b or augmented view 1340 b. Hence,the surgeon 1390 can be provided with two different versions of areal-time view, namely microscope view 1320 b and augmented image 1330b, or microscope view 1320 b and augmented image 1340 b. According tosome embodiments, the OCT image 1360 b can be registered with themicroscope view 1320 b or the microscope image 1350 b. According to someembodiments, an actual target location is not visible in the microscopeview 1320 b or the microscope image 1350 b. According to someembodiments, the augmented image (1330 b or 1340 b) enables the surgeon1390 b to perceive information regarding a relative position of a distalend of an elongate probe with respect to the target location when thedistal end of the elongate probe is not visible in the microscope view1320 b or the microscope image 1350 b.

In some embodiments, the surgeon 1390 b views the microscope image 1320b when initially inserting a treatment probe into the anterior chamberof the patient's eye. Subsequently, an OCT image 1360 b (e.g. showingcollector channels or networks) can be overlaid to the microscope image1320 b, for example using registration techniques as discussed elsewhereherein. The surgeon may then decide where to deliver the treatments(e.g. laser ablation energy applied to trabecular meshwork,juxtacanalicular trabecular meshwork, and inner wall of Schlemm'scanal). In some cases, this may involve the surgeon using a graphicalvisual element or a treatment reference marker to label or mark thetreatment location. In some cases, a computerized system may make thedetermination of where to place a graphical visual element or treatmentreference marker. Subsequent to the above steps, the surgeon can move orposition the treatment probe within the anterior chamber of the eye, anda subsequent OCT imaging protocol can be used to facilitate (e.g. viaoverlays of graphical visual elements) guiding or navigation of theprobe to a target or desired treatment location. In some cases,graphical visual elements can be overlaid to a microscope view or imageprior to placing the probe in the anterior chamber. In some cases,graphical visual elements can be overlaid to a microscope view or imagesubsequent to placing the probe in the anterior chamber. In some cases,graphical visual elements can be overlaid to an OCT image prior toplacing the probe in the anterior chamber. In some cases, graphicalvisual elements can be overlaid to an OCT image subsequent to placingthe probe in the anterior chamber.

The controlling unit 410 (e.g. as depicted in FIG. 4, 5, 8, 10, or 11)may comprise one or more processors (e.g. such as processor 1405depicted in FIG. 14) configured with instructions for perform one ormore steps illustrated in FIGS. 13, 13A, and 13B, and operations asdescribed elsewhere herein. Similarly, the controlling unit 410 mayinclude or be in connectivity with any other component of a computersystems (e.g. such as computer system 1401 depicted in FIG. 14).

Although certain methods and apparatus disclosed herein are described inthe context of ablation, the user interface and display can beconfigured to direct surgical placement of implants as described herein.For example, the target locations can be shown with reference to thecollector channels, and the surgical placement of an implant can bedirected to a target location near Schlemm's canal, for example. Thearrows and other features shown on the heads up display can be used todirect placement of a plurality of locations of a plurality of surgicalimplants to be placed in the eye, for example implants to createopenings to Schlemm's canal. The implant can be placed by creating anopening into Schlemm's canal mechanically (e.g. with a sharp instrument)and placing the implant at the target location, for example.

Each of the calculations or operations described herein may be performedusing a computer or other processor having hardware, software, and/orfirmware. The various method steps may be performed by modules, and themodules may comprise any of a wide variety of digital and/or analog dataprocessing hardware and/or software arranged to perform the method stepsdescribed herein. The modules may optionally include data processinghardware adapted to perform one or more of these steps by havingappropriate machine programming code associated therewith, the modulesfor two or more steps (or portions of two or more steps) beingintegrated into a single processor board or separated into differentprocessor boards in any of a wide variety of integrated and/ordistributed processing architectures. These methods and systems willoften employ a tangible media embodying machine-readable code withinstructions for performing method steps as describe elsewhere herein.All features of the described systems are applicable to the describedmethods mutatis mutandis, and vice versa.

The processor may be a hardware processor such as a central processingunit (CPU), a graphic processing unit (GPU), or a general-purposeprocessing unit. The processor can be any suitable integrated circuits,such as computing platforms or microprocessors, logic devices and thelike. Although the disclosure is described with reference to aprocessor, other types of integrated circuits and logic devices are alsoapplicable. The processors or machines may not be limited by the dataoperation capabilities. The processors or machines may perform 512 bit,256 bit, 128 bit, 64 bit, 32 bit, or 16 bit data operations.

In some embodiments, the processor may be a processing unit of acomputer system. FIG. 14 shows a computer system 1401 that can beconfigured to implement any computing system or method disclosed in thepresent application. The computer system 1401 can comprise a mobilephone, a tablet, a wearable device, a laptop computer, a desktopcomputer, a central server, or the like.

The computer system 1401 includes a central processing unit (CPU, also“processor” and “computer processor” herein) 1405, which can be a singlecore or multi core processor, or a plurality of processors for parallelprocessing. The CPU can be the processor as described above. Thecomputer system 1401 also includes memory or memory location 1410 (e.g.,random-access memory, read-only memory, flash memory), electronicstorage unit 1415 (e.g., hard disk), communication interface 1420 (e.g.,network adapter) for communicating with one or more other systems, andperipheral devices 1425, such as cache, other memory, data storageand/or electronic display adapters. In some cases, the communicationinterface may allow the computer to be in communication with anotherdevice such as the imaging device or audio device. The computer may beable to receive input data from the coupled devices for analysis. Thememory 1410, storage unit 1415, interface 1420 and peripheral devices1425 are in communication with the CPU 1405 through a communication bus(solid lines), such as a motherboard. The storage unit 1415 can be adata storage unit (or data repository) for storing data. The computersystem 1401 can be operatively coupled to a computer network (“network”)1430 with the aid of the communication interface 1420. The network 1430can be the Internet, an Internet and/or extranet, or an intranet and/orextranet that is in communication with the Internet. The network 1430 insome cases is a telecommunication and/or data network. The network 1430can include one or more computer servers, which can enable distributedcomputing, such as cloud computing. The network 1430, in some cases withthe aid of the computer system 1401, can implement a peer-to-peernetwork, which may enable devices coupled to the computer system 1401 tobehave as a client or a server.

The CPU 1405 can execute a sequence of machine-readable instructions,which can be embodied in a program or software. The instructions may bestored in a memory location, such as the memory 1410. The instructionscan be directed to the CPU 1405, which can subsequently program orotherwise configure the CPU 1405 to implement methods of the presentdisclosure. Examples of operations performed by the CPU 1405 can includefetch, decode, execute, and writeback.

The CPU 1405 can be part of a circuit, such as an integrated circuit.One or more other components of the system 1401 can be included in thecircuit. In some cases, the circuit is an application specificintegrated circuit (ASIC).

The storage unit 1415 can store files, such as drivers, libraries andsaved programs. The storage unit 1415 can store user data, e.g., userpreferences and user programs. The computer system 1401 in some casescan include one or more additional data storage units that are externalto the computer system 1401, such as located on a remote server that isin communication with the computer system 1401 through an intranet orthe Internet.

The computer system 1401 can communicate with one or more remotecomputer systems through the network 1430. For instance, the computersystem 1401 can communicate with a remote computer system of a user.Examples of remote computer systems include personal computers, slate ortablet PC's, smart phones, personal digital assistants, and so on. Theuser can access the computer system 1401 via the network 1430.

Methods as described herein can be implemented by way of machine (e.g.,computer processor) executable code stored on an electronic storagelocation of the computer system 1401, such as, for example, on thememory 1410 or electronic storage unit 1415. The machine executable ormachine readable code can be provided in the form of software. Duringuse, the code can be executed by the processor 1405. In some cases, thecode can be retrieved from the storage unit 1415 and stored on thememory 1410 for ready access by the processor 1405. In some situations,the electronic storage unit 1415 can be precluded, andmachine-executable instructions are stored on memory 1410.

The code can be pre-compiled and configured for use with a machinehaving a processer adapted to execute the code, or can be compiledduring runtime. The code can be supplied in a programming language thatcan be selected to enable the code to execute in a pre-compiled oras-compiled fashion.

Aspects of the systems and methods provided herein, such as the computersystem 1401, can be embodied in programming Various aspects of thetechnology may be thought of as “products” or “articles of manufacture”typically in the form of machine (or processor) executable code and/orassociated data that is carried on or embodied in a type of machinereadable medium. Machine-executable code can be stored on an electronicstorage unit, such as memory (e.g., read-only memory, random-accessmemory, flash memory) or a hard disk. “Storage” type media can includeany or all of the tangible memory of the computers, processors or thelike, or associated modules thereof, such as various semiconductormemories, tape drives, disk drives and the like, which may providenon-transitory storage at any time for the software programming. All orportions of the software may at times be communicated through theInternet or various other telecommunication networks. Suchcommunications, for example, may enable loading of the software from onecomputer or processor into another, for example, from a managementserver or host computer into the computer platform of an applicationserver. Thus, another type of media that may bear the software elementsincludes optical, electrical and electromagnetic waves, such as usedacross physical interfaces between local devices, through wired andoptical landline networks and over various air-links. The physicalelements that carry such waves, such as wired or wireless links, opticallinks or the like, also may be considered as media bearing the software.As used herein, unless restricted to non-transitory, tangible “storage”media, terms such as computer or machine “readable medium” refer to anymedium that participates in providing instructions to a processor forexecution.

Hence, a machine readable medium, such as computer-executable code, maytake many forms, including but not limited to, a tangible storagemedium, a carrier wave medium or physical transmission medium.Non-volatile storage media include, for example, optical or magneticdisks, such as any of the storage devices in any computer(s) or thelike, such as may be used to implement the databases, etc. shown in thedrawings. Volatile storage media include dynamic memory, such as mainmemory of such a computer platform. Tangible transmission media includecoaxial cables; copper wire and fiber optics, including the wires thatcomprise a bus within a computer system. Carrier-wave transmission mediamay take the form of electric or electromagnetic signals, or acoustic orlight waves such as those generated during radio frequency (RF) andinfrared (IR) data communications. Common forms of computer-readablemedia therefore include for example: a floppy disk, a flexible disk,hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD orDVD-ROM, any other optical medium, punch cards paper tape, any otherphysical storage medium with patterns of holes, a RAM, a ROM, a PROM andEPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wavetransporting data or instructions, cables or links transporting such acarrier wave, or any other medium from which a computer may readprogramming code and/or data. Many of these forms of computer readablemedia may be involved in carrying one or more sequences of one or moreinstructions to a processor for execution.

The computer system 1401 can include or be in communication with anelectronic display 1435 that comprises a user interface 1440 forproviding, for example, a management interface. Examples of UI'sinclude, without limitation, a graphical user interface (GUI) andweb-based user interface. The user interface 1440 may be the same as theuser interface 413 as described in FIG. 4. Alternatively, the userinterface may be a separate user interface.

The computer system 1401 may comprise various other computer componentsto facilitate communication with an external device such as themicroscope system, camera, OCT unit, laser unit, external processor ormemory. The communication modules may include suitable means forinstruction and data transfer such as double data rate. Various meanscan be employed for communication such as peripheral componentinterconnect card, computer buses including but not limited to PCIexpress, PCI-X, HyperTransport, and so forth. Suitable communicationmeans may be selected according to the requirements of the bandwidth andcompatibility of the external device and the central processing unit1405. For example, one data bus may be for command transfer (e.g.,AXI4lite bus) to the laser unit 31 and a different data bus (e.g., AXI4bus) may be used for image data transfer. Alternatively or additionally,wireless communication may be employed.

Methods and systems of the present disclosure can be implemented by wayof one or more algorithms. An algorithm can be implemented by way ofsoftware upon execution by the central processing unit 1405.

As used here, the terms “overlay”, “overlaid”, “superimpose”,“superimposed”, and the like, may in some embodiments also encompassother image or information combining techniques, including “underlay”,“underlaid”, “subjacent”, and similar approaches. It will be appreciatedthat composite or fused images, views, information, or displays, whichmay combine or blend images, graphical visual elements, and/orinformation, or the like, which may be present in a single layer ormultiple layers, can be generated or provided by any of thesetechniques.

Any of the system, device, or method embodiments disclosed herein mayinvolve or include the use systems, devices, or methods such as thosedisclosed in U.S. Patent Publication Nos. 2004/0082939, 2012/0283557,2016/0095751, and 2017/0202708, and U.S. Pat. Nos. 4,846,172, 6,251,103,8,540,659, 8,679,089, 9,603,741, 9,642,746, 9,820,883, and 9,833,357,the contents of each of which are incorporated herein by reference.

Although reference is made to determining locations of collectorchannels with markers shown on a display, the eye can be marked prior tosurgery at locations corresponding to the collector channels using themethods and apparatus as disclosed herein. The surgeon can use thesemarkings to create openings to Schlemm's canal in response to themarkings placed on the eye. For example, the eye can be marked with inkto identify locations of preferred surgical treatment, and the openingscreated in the trabecular meshwork at locations corresponding to thepreferred surgical treatment. While preferred embodiments of the presentinvention have been shown and described herein, it will be obvious tothose skilled in the art that such embodiments are provided by way ofexample only. Numerous variations, changes, and substitutions will nowoccur to those skilled in the art without departing from the invention.It should be understood that various alternatives to the embodiments ofthe invention described herein may be employed in practicing theinvention. It is intended that the following claims define the scope ofthe invention and that methods and structures within the scope of theseclaims and their equivalents be covered thereby.

What is claimed is:
 1. A system for treating glaucoma in an eye, thesystem comprising: a probe that is insertable into an anterior chamberof an eye, the probe including at least one optical fiber configured totransmit photoablation energy sufficient to photoablate tissue, theprobe defining a probe axis that extends from a distal portion of theprobe, the probe further configured to perform real-time opticalcoherence tomography (OCT) data collection from tissue distal to thedistal portion of the probe; a viewing device; and at least oneprocessor coupled to the probe and the viewing device, the at least oneprocessor configured to: generate an OCT data stream from the real-timeOCT data collection of the probe; collect, from the probe when the probehas been inserted into the anterior chamber of the eye and is positionedand repositioned within the anterior chamber, first OCT data from theOCT data stream, the first OCT data representing a tissue structure ofthe eye, the first OCT data updating in real-time as the probe isrepositioned; determine, from the first OCT data, locations of atrabecular meshwork of the eye relative to the probe and a Schlemm'scanal of the eye relative to the probe, the locations updating inreal-time as the probe is repositioned; display, on the viewing device,based on the determined locations, instructions for repositioning theprobe such that the distal portion of the probe contacts the trabecularmeshwork and the probe axis extends toward the Schlemm's canal, theinstructions updating in real-time as the probe is repositioned;determine, from the first OCT data, that the probe is positioned suchthat the distal portion of the probe contacts the trabecular meshworkand the probe axis extends toward the Schlemm's canal; collect, from theprobe when the probe is in contact with the trabecular meshwork, secondOCT data from the OCT data stream, the second OCT data representing thetissue structure of the eye as a first channel is formed viaphotoablation through the trabecular meshwork, through ajuxtacanalicular trabecular meshwork of the eye, and through an innerwall of the Schlemm's canal, the second OCT data updating in real-timeas the first channel is formed; determine, from the second OCT data,that the first channel has extended through the inner wall of theSchlemm's canal; and display, on the viewing device, an indication thatthe first channel has extended through the inner wall of the Schlemm'scanal.
 2. A method for treating glaucoma in an eye, the methodcomprising: inserting a probe into an anterior chamber of an eye, theprobe including at least one optical fiber configured to transmitphotoablation energy sufficient to photoablate tissue, the probedefining a probe axis that extends from a distal portion of the probe,the probe further configured to perform real-time optical coherencetomography (OCT) data collection from tissue distal to the distalportion of the probe; generating an OCT data stream from the real-timeOCT data collection of the probe; collecting, from the probe when theprobe has been inserted into the anterior chamber of the eye and ispositioned and repositioned within the anterior chamber, first OCT datafrom the OCT data stream, the first OCT data representing a tissuestructure of the eye, the first OCT data updating in real-time as theprobe is repositioned; determining, from the first OCT data, locationsof a trabecular meshwork of the eye relative to the probe and aSchlemm's canal of the eye relative to the probe, the locations updatingin real-time as the probe is repositioned; displaying, based on thedetermined locations, instructions for repositioning the probe such thatthe distal portion of the probe contacts the trabecular meshwork and theprobe axis extends toward the Schlemm's canal, the instructions updatingin real-time as the probe is repositioned; determining, from the firstOCT data, that the probe is positioned such that the distal portion ofthe probe contacts the trabecular meshwork and the probe axis extendstoward the Schlemm's canal; collecting, from the probe when the probe isin contact with the trabecular meshwork, second OCT data from the OCTdata stream, the second OCT data representing the tissue structure ofthe eye as a first channel is formed via photoablation through thetrabecular meshwork, through a juxtacanalicular trabecular meshwork ofthe eye, and through an inner wall of the Schlemm's canal, the secondOCT data updating in real-time as the first channel is formed;determining, from the second OCT data, that the first channel hasextended through the inner wall of the Schlemm's canal; and displayingan indication that the first channel has extended through the inner wallof the Schlemm's canal.
 3. The system of claim 1, wherein the at leastone processor is further configured such that the instructions forrepositioning the probe include a graphical element that is configuredto change dynamically based on a position and an orientation of theprobe.
 4. The system of claim 1, wherein the at least one processor isfurther configured such that the instructions for repositioning theprobe include at least one graphical visual element positioned to showat least one of a relative distance between the distal portion of theprobe and the trabecular meshwork, a relative distance between thedistal portion of the probe and the juxtacanalicular trabecularmeshwork, or a relative distance between the distal portion of the probeand the inner wall of the Schlemm's canal.
 5. The system of claim 1,wherein the indication that the first channel has extended through theinner wall of the Schlemm's canal comprises a graphical visual elementthat illustrates that the first channel has extended through the innerwall of the Schlemm's canal.
 6. The system of claim 1, furthercomprising an optical microscope positioned external to the eye andconfigured to use visible light to form a real-time image of the eye onthe viewing device, the real-time image lacking the trabecular meshworkand the Schlemm's canal due to total internal reflection of the visiblelight from a cornea of the eye.
 7. The system of claim 6, wherein theviewing device is viewable through oculars of the optical microscope. 8.The system of claim 6, wherein the optical microscope is furtherconfigured to form the real-time image of the eye without using agoniolens.
 9. The system of claim 6, wherein the viewing device isconfigured to display a graphical visual element corresponding to aninner wall of the Schlemm's canal in addition to the real-time image ofthe eye.
 10. The system of claim 6, wherein the viewing device isseparate from the optical microscope.
 11. The system of claim 1, whereinthe at least one processor is further configured to: determine, from thefirst OCT data, a thickness of the trabecular meshwork; and display, onthe viewing device, data corresponding to the determined thickness ofthe trabecular meshwork.
 12. The system of claim 11, wherein the datacorresponding to the determined thickness of the trabecular meshwork isconfigured to allow a determination whether the trabecular meshwork issufficiently compressed based on the first OCT data.
 13. The system ofclaim 1, wherein the at least one processor is further configured to:display, on the viewing device, instructions for repositioning the probesuch that the distal portion of the probe contacts the trabecularmeshwork and the probe axis extends toward the Schlemm's canal and isdirected toward a second location, different from the first location, onthe Schlemm's canal, the instructions updating in real-time as the probeis repositioned; determine that the probe is positioned such that thedistal portion of the probe contacts the trabecular meshwork and theprobe axis extends toward the second location on the Schlemm's canal;determine that a second channel has extended through the inner wall ofthe Schlemm's canal; and display, on the viewing device, an indicationthat the second channel has extended through the inner wall of theSchlemm's canal.
 14. The system of claim 1, wherein the probe axis isconfigured to extend toward the Schlemm's canal based on a location in atarget tissue region, the location including at least one of a region ina collector channel network, a fields that is more dense, a field thatcontains larger vessels, a field that contains a larger distribution ofvessels, a field that contains vessels that are less obstructed, or afield that correspond to circumferential flow areas provided by theSchlemm's canal.
 15. The method of claim 2, further comprising forming,with an optical microscope positioned external to the eye and configuredto use visible light a real-time image of the eye, the real-time imagelacking the trabecular meshwork and the Schlemm's canal due to totalinternal reflection of the visible light from a cornea of the eye. 16.The method of claim 2, wherein the instructions for repositioning theprobe include at least one graphical visual element positioned to showat least one of a relative distance between the distal portion of theprobe and the trabecular meshwork, a relative distance between thedistal portion of the probe and the juxtacanalicular trabecularmeshwork, or a relative distance between the distal portion of the probeand the inner wall of the Schlemm's canal.
 17. The method of claim 16,wherein the indication that the first channel has extended through theinner wall of the Schlemm's canal comprises a graphical visual elementthat illustrates that the first channel has extended through the innerwall of the Schlemm's canal.
 18. The method of claim 15, furthercomprising forming the real-time image of the eye without using agoniolens.
 19. A system for treating glaucoma in an eye, the systemcomprising: a probe that is insertable into an anterior chamber of aneye, the probe including an optical fiber configured to transmitphotoablation energy sufficient to photoablate tissue, the probedefining a probe axis that extends from a distal portion of the probe,the probe further configured to perform real-time optical coherencetomography (OCT) data collection, using the optical fiber, from tissuedistal to the distal portion of the probe; a viewing device; and atleast one processor coupled to the probe and the viewing device, the atleast one processor configured to: generate an OCT data stream from thereal-time OCT data collection of the probe; collect, from the probe whenthe probe has been inserted into the anterior chamber of the eye and ispositioned and repositioned within the anterior chamber, first OCT datafrom the OCT data stream, the first OCT data representing a tissuestructure of the eye, the first OCT data updating in real-time as theprobe is repositioned; determine, from the first OCT data, locations ofa trabecular meshwork of the eye relative to the probe and a Schlemm'scanal of the eye relative to the probe, the locations updating inreal-time as the probe is repositioned; display, on the viewing device,based on the determined locations, instructions for repositioning theprobe in three dimensions such that the distal portion of the probecontacts the trabecular meshwork and the probe axis extends toward theSchlemm's canal, the instructions for repositioning the probe includinggraphical visual elements positioned to show relative distances betweenthe distal portion of the probe and at least one of the trabecularmeshwork, the juxtacanalicular trabecular meshwork, and the inner wallof the Schlemm's canal, the instructions updating in real-time as theprobe is repositioned; determine, from the first OCT data, that theprobe is positioned such that the distal portion of the probe contactsthe trabecular meshwork and the probe axis extends toward the Schlemm'scanal; collect, from the probe when the probe is in contact with thetrabecular meshwork, second OCT data from the OCT data stream, thesecond OCT data representing the tissue structure of the eye as a firstchannel is formed via photoablation through the trabecular meshwork,through a juxtacanalicular trabecular meshwork of the eye, and throughan inner wall of the Schlemm's canal, the second OCT data updating inreal-time as the first channel is formed; determine, from the second OCTdata, that the first channel has extended through the inner wall of theSchlemm's canal; and display, on the viewing device, an indication thatthe first channel has extended through the inner wall of the Schlemm'scanal.